Publications by authors named "Ahmed Al-Harrasi"

197 Publications

Green synthesis and biomedicinal applications of silver and gold nanoparticles functionalized with methanolic extract of .

Artif Cells Nanomed Biotechnol 2021 Dec;49(1):194-203

Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, Sultanate of Oman.

This study deals with facile and rapid synthesis of silver nanoparticles (AgNPs) and Gold nanoparticles (AuNPs) using leaves extracts (MLE). The synthesized AgNPs and AuNPs were characterized by UV-visible spectroscopy (UV-Vis), Fourier transformed infra-red spectroscopy (FT-IR), atomic force microscopy (AFM) and transmission electron microscopy (TEM) techniques. The phytochemical analysis showed the presence of bioactive secondary metabolites, which are involved in the synthesis of nanoparticles (NPs). The surface plasmon resonance (SPR) observed at 435 and 550 nm, confirmed the green synthesis of AgNPs and AuNPs, respectively. The TEM images showed poly dispersed and round oval shapes of Ag and Au NPs with an average particles size of 10.23 ± 2 nm and 13.45 ± 2 nm, respectively. TEM results are in close agreements with that of AFM analysis. The FT-IR spectroscopy revealed the presence of OH, -NH and C = O groups, which involved in the synthesis of NPs. The MLE and their AgNPs and AuNP exhibited good antibacterial and anti-oxidant activities. Moreover, MLE and NPs also showed analgesic activities in mice, and excellent sedative properties in open field test paradigm.
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http://dx.doi.org/10.1080/21691401.2021.1890099DOI Listing
December 2021

Therapeutic potential of N-substituted thiosemicarbazones as new urease inhibitors: Biochemical and in silico approach.

Bioorg Chem 2021 Feb 2;109:104691. Epub 2021 Feb 2.

Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800, Pakistan. Electronic address:

Urease enzyme plays a key role in pathogenesis of gastritis and peptic ulcers. Its inhibition averts our bodies from many disorders including formation of urinary calculi. In agriculture, the high urease content causes severe environmental and hence economic problems. Due to deficiency of effective and safer drugs to tackle the aforementioned disorders, the quest for new scaffolds becomes mandatory in the field of medicinal chemistry. In this regard, we herein report a new series of N-substituted thiosemicarbazones 3a-v as potential candidates for urease inhibition. These new N-substituted thiosemicarbazones 3a-v of distant chemical scaffolds were characterized by advanced spectroscopic techniques, such as FTIR, HNMR, CNMR, ESI-MS and in the case of compound 3g by single crystal X-ray analysis. The compounds were evaluated for their urease inhibitory potential. All newly synthesized compounds showed significant urease inhibitions with IC values in range of 2.7 ± 0.320-109.2 ± 3.217 μM. Molecular docking studies were used for interactions pattern and structure-activity relationship for all compounds, which demonstrated excellent binding interactions with the active site residues, such as hydrogen bonding, π-π interactions, π-H and nickel atom coordination.
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http://dx.doi.org/10.1016/j.bioorg.2021.104691DOI Listing
February 2021

Mangrove tree (Avicennia marina): insight into chloroplast genome evolutionary divergence and its comparison with related species from family Acanthaceae.

Sci Rep 2021 Feb 11;11(1):3586. Epub 2021 Feb 11.

Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, 616, Oman.

Avicennia marina (family Acanthaceae) is a halotolerant woody shrub that grows wildly and cultivated in the coastal regions. Despite its importance, the species suffers from lack of genomic datasets to improve its taxonomy and phylogenetic placement across the related species. Here, we have aimed to sequence the plastid genome of A. marina and its comparison with related species in family Acanthaceae. Detailed next-generation sequencing and analysis showed a complete chloroplast genome of 150,279 bp, comprising 38.6% GC. Genome architecture is quadripartite revealing large single copy (82,522 bp), small single copy (17,523 bp), and pair of inverted repeats (25,117 bp). Furthermore, the genome contains 132 different genes, including 87 protein-coding genes, 8 rRNA, 37 tRNA genes, and 126 simple sequence repeats (122 mononucleotide, 2 dinucleotides, and 2 trinucleotides). Interestingly, about 25 forward, 15 reversed and 14 palindromic repeats were also found in the A. marina. High degree synteny was observed in the pairwise alignment with related genomes. The chloroplast genome comparative assessment showed a high degree of sequence similarity in coding regions and varying divergence in the intergenic spacers among ten Acanthaceae species. The pairwise distance showed that A. marina exhibited the highest divergence (0.084) with Justicia flava and showed lowest divergence with Aphelandra knappiae (0.059). Current genomic datasets are a valuable resource for investigating the population and evolutionary genetics of family Acanthaceae members' specifically A. marina and related species.
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http://dx.doi.org/10.1038/s41598-021-83060-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878759PMC
February 2021

Attenuation of nociceptive and paclitaxel-induced neuropathic pain by targeting inflammatory, CGRP and substance P signaling using 3-Hydroxyflavone.

Neurochem Int 2021 Mar 5;144:104981. Epub 2021 Feb 5.

Natural and Medical Sciences Research Center, University of Nizwa, Birkat-ul-Mouz 616, Nizwa, Oman. Electronic address:

Paclitaxel is an anti-microtubule agent, most widely used chemotherapeutic agent for the treatment of malignant solid tumors. However, it is associated with some severe side effects including painful neurotoxicity with reporting of neuropathic pain and sensory abnormalities by patients during and after paclitaxel therapy. Peripheral neuropathy was induced by the administration of paclitaxel (4 mg/kg on days 1, 3, 5, and 7). In this study, the anti-nociceptive and anti-inflammatory propensity of 3-Hydroxyflavone (3HF) in mice and the preventive effect of 3HF against paclitaxel-induced peripheral neuropathy in Sprague Dawley (SD) rats were investigated. Moreover, tactile and cold allodynia, thermal and tail immersion hyperalgesia, and effects on motor-coordination were also evaluated. Furthermore, the expression of proinflammatory cytokines i.e. Calcitonin gene-related peptide (CGRP), and Substance P from the spinal cord was examined through RT-PCR. Additionally, a computational structural biology approach was applied to search the potential therapeutic targets and to predict the binding mechanism of 3HF. Treatment of 3HF alleviated the nociceptive pain, paw edema, development of tactile and cold allodynia, and hyperalgesia. Similarly, treatment with 3HF suppressed the paclitaxel-induced increase in mRNA expression of several inflammatory cytokines including tumor necrosis factor -α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), CGRP, and Substance P. However, the daily treatment of 3HF did not affect the motor behaviors of rats. The inhibitory mechanism of 3HF in neuropathic pain is predicted with extensive computational bioinformatics approach which indicates that the 3HF effectively interacts with the binding domains of Nuclear factor-kappa B (NF-κB), CGRP receptor and the receptor of Substance P to exert its inhibitory activities. However, the computationally predicted binding affinities revealed that the potential of binding of the compound with Substance P receptor (Neurokinin 1 receptor) is higher than the other receptors; there NK1R could be the most possible binding target of 3HF. These findings indicate that 3HF has anti-nociceptive, anti-inflammatory, and anti-neuropathic pain effects against paclitaxel-induced neuropathic pain.
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http://dx.doi.org/10.1016/j.neuint.2021.104981DOI Listing
March 2021

Biosynthetic diversity in triterpene cyclization within the Boswellia genus.

Phytochemistry 2021 Jan 29;184:112660. Epub 2021 Jan 29.

Department of Organic Chemistry, Martin-Luther University Halle-Wittenberg, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.

This review is not intended to describe the triterpenes isolated from the Boswellia genus, since this information has been covered elsewhere. Instead, the aim is to provide insights into the biosynthesis of triterpenes in Boswellia. This genus, which has 24 species, displays fascinating structural diversity and produces a number of medicinally important triterpenes, particularly boswellic acids. Over 300 volatile components have been reported in the essential oil of Boswellia, and more than 100 diterpenes and triterpenes have been isolated from this genus. Given that no triterpene biosynthetic enzymes have yet been isolated from any members of the Boswellia genus, this review will cover the likely biosynthetic pathways as inferred from structures in nature and the probable types of biosynthetic enzymes based on knowledge of triterpene biosynthesis in other plant species. It highlights the importance of frankincense and the factors and threats affecting its production. It covers triterpene biosynthesis in the genus Boswellia, including dammaranes, tirucallic acids, lupanes, oleananes, ursanes and boswellic acids. Strategies for elucidating triterpene biosynthetic pathways in Boswellia are considered. Furthermore, the possible mechanisms behind wound-induced resin synthesis by the tree and related gene expression profiling are covered. In addition, the influence of the environment and the genotype on the biosynthesis of resin and on variations in the compositions and types of resins will also be reviewed.
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http://dx.doi.org/10.1016/j.phytochem.2021.112660DOI Listing
January 2021

Motor signs in Alzheimer's disease and vascular dementia: Detection through natural language processing, co-morbid features and relationship to adverse outcomes.

Exp Gerontol 2021 Apr 12;146:111223. Epub 2021 Jan 12.

King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK; South London and Maudsley NHS Foundation Trust, London, UK. Electronic address:

Background: Motor signs in patients with dementia are associated with a higher risk of cognitive decline, institutionalisation, death and increased health care costs, but prevalences differ between studies. The aims of this study were to employ a natural language processing pipeline to detect motor signs in a patient cohort in routine care; to explore which other difficulties occur co-morbid to motor signs; and whether these, as a group and individually, predict adverse outcomes.

Methods: A cohort of 11,106 patients with dementia in Alzheimer's disease, vascular dementia or a combination was assembled from a large dementia care health records database in Southeast London. A natural language processing algorithm was devised in order to establish the presence of motor signs (bradykinesia, Parkinsonian gait, rigidity, tremor) recorded around the time of dementia diagnosis. We examined the co-morbidity profile of patients with these symptoms and used Cox regression models to analyse associations with survival and hospitalisation, adjusting for twenty-four potential confounders.

Results: Less than 10% of patients were recorded to display any motor sign, and tremor was most frequently detected. Presence of motor signs was associated with younger age at diagnosis, neuropsychiatric symptoms, poor physical health and higher prescribing of psychotropics. Rigidity was independently associated with a 23% increased mortality risk after adjustment for confounders (p = 0.014). A non-significant trend for a 15% higher risk of hospitalisation was detected in those with a recorded Parkinsonian gait (p = 0.094).

Conclusions: With the exception of tremor, motor signs appear to be under-recorded in routine care. They are part of a complex clinical picture and often accompanied by neuropsychiatric and functional difficulties, and thereby associated with adverse outcomes. This underlines the need to establish structured examinations in routine clinical practice via easy-to-use tools.
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http://dx.doi.org/10.1016/j.exger.2020.111223DOI Listing
April 2021

Novel Anticancer Dimeric Napthoquiones from Diospyros lotus Having Anti-Tumor, Anti-Inflammatory and Multidrug Resistance Reversal Potential: In Vitro, In Vivo and In Silico Evidence.

Anticancer Agents Med Chem 2021 Jan 11. Epub 2021 Jan 11.

Natural and Medical Sciences Research Center, University of Nizwa, Birkat-ul-Mouz 616, Nizwa. Oman.

Background: Cancer being a genetically heterogenous and complex disease and the available therapies are not very effective, rendering them the predominant cause of mortality across the world. The discovery of new anticancer drugs with higher efficacy and milder side effects is a great challenge for health professionals.

Objective: The current study focused on anticancer potential of two known dimeric napthoquiones, diospyrin (1) and 8-hydroxydiospyrin (2) isolated from the roots of Diospyros lotus.

Methods: In-vitro Epstein-Barr-Virus (EVA) early antigen activation assay was used to evaluate the antitumor potential of test compounds followed by two-stage carcinogenesis assay on mouse skin for anti-carcinogenic effect. Compounds were also assessed for their multidrug resistance reversal potential. The in-vitro heat induced protein denaturation assay was used for the anti-inflammatory effect of the test compounds.

Results: Both compounds evoked marked cytotoxic activity with IC50 of 47.40 and 36.91 ppm, respectively. In Epstein-Barr-Virus (EVA) early antigen activation assay compounds 1 and 2 showed IC50 values of 426 ppm and 412 ppm, respectively. The tested compounds showed 60% survival rate of the lymphoblastoid Raji cells at a concentration of 1000 (mol / ratio 32 pmol TPA). In two-stage carcinogenesis assay on mouse skin, both compounds significantly delayed the formation of papillomas on mouse skin. Compound 1 showed 50% effect at 14th weeks, whereas compound 2 exerted the same effect at 13th weeks, while both provoked 100% effect at 20th weeks. Both compounds significantly attenuated thermal induced protein denaturation with EC50 values of 298 and 264 µg/mL, respectively. The dimeric napthoquiones were evaluated for their effects on the reversion of multidrug resistant (MDR) cell lines mediated by P-glycoprotein using rhodamine 123 dye-based exclusion screening test on human mdr1 gene transfected thymic lymphoma L5178 cell line. The compounds 1 and 2 exhibited promising MDR reversal effect in a dose-dependent manner against mouse Tlymphoma cell line. Docking results also showed that both compounds have good docking statistics as compared with standard.

Conclusions: Both the compounds demonstrated marked anti-tumor, anti-carcinogenic, and MDR reversal effects with significant attenuation of thermal induced denaturation of protein. These compounds may explain the traditional uses of D. lotus and might be effective anticancer agents.
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http://dx.doi.org/10.2174/1871520621666210112113127DOI Listing
January 2021

Botanical drugs and supplements affecting the immune response in the time of COVID-19: Implications for research and clinical practice.

Phytother Res 2020 Dec 29. Epub 2020 Dec 29.

School of Pharmacy, University of Reading, Reading, UK.

In times of health crisis, including the current COVID-19 pandemic, the potential benefit of botanical drugs and supplements emerges as a focus of attention, although controversial efficacy claims are rightly a concern. Phytotherapy has an established role in everyday self-care and health care, but, since botanical preparations contain many chemical constituents rather than single compounds, challenges arise in demonstrating efficacy and safety. However, there is ample traditional, empirical, and clinical evidence that botanicals can offer some protection and alleviation of disease symptoms as well as promoting general well-being. Newly emerging viral infections, specifically COVID-19, represent a unique challenge in their novelty and absence of established antiviral treatment or immunization. We discuss here the roles and limitations of phytotherapy in helping to prevent and address viral infections, especially regarding their effects on immune response. Botanicals with a documented immunomodulatory, immunostimulatory, and antiinflammatory effects include adaptogens, Boswellia spp., Curcuma longa, Echinacea spp., Glycyrrhiza spp., medicinal fungi, Pelargonium sidoides, salicylate-yielding herbs, and Sambucus spp. We further provide a clinical perspective on applications and safety of these herbs in prevention, onset, progression, and convalescence from respiratory viral infections.
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http://dx.doi.org/10.1002/ptr.7008DOI Listing
December 2020

Macrocyclic sulfone derivatives: Synthesis, characterization, in vitro biological evaluation and molecular docking.

Drug Dev Res 2020 Dec 23. Epub 2020 Dec 23.

Department of Chemistry, University of Malakand, Chakdara 18800, Dir Lower, Khyber Pakhtunkhwa, Pakistan.

An artificial series of macrocycles based on 4,4'-sulfonyldiphenol intermediate was synthesized using a multistep procedure involving oxidation of bisphenol sulfide, etherification of phenolic hydroxyl groups, and final ring closure with different diamines. Different chemical species having aromatic, heteroaromatic, and aliphatic characters were incorporated into macrocyclic frameworks in the final step of ring closure. This simple and easily executable synthetic strategy was applied to synthesize 15 macrocycles (5a-o) in excellent yields. Characterization of the synthesized products was achieved through well-known modern spectroscopic techniques such as IR, NMR, and Mass. Macrocycles 5m and 5n were found to show significant AChE inhibition with IC values of 76.9 ± 0.24 and 71.2 ± 0.77 μM, respectively. Macrocycle 5n was also found to be an active inhibitor of butyrylcholinesterase (BChE) with IC score of 55.3 ± 0.54 μM. Among others, macrocycle 5l cyclized with o-phenylenediamine demonstrated moderate inhibition with IC value of 81.1 ± 0.54 μM. Increasing interest in studying interactions of macrocycles with different enzymatic targets compelled us to design and synthesize sulfone-based macrocycles that might prove as highly potent class of biologically active compounds.
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http://dx.doi.org/10.1002/ddr.21775DOI Listing
December 2020

Molecular epidemiology of COVID-19 in Oman: A molecular and surveillance study for the early transmission of COVID-19 in the country.

Int J Infect Dis 2021 Jan 13;104:139-149. Epub 2021 Jan 13.

Natural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, PC 616 Nizwa, Oman. Electronic address:

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been proven to be lethal to human health, which affects almost every corner of the world. The objectives of this study were to add context to the global data and international genomic consortiums, and to give insight into the efficiency of the contact tracing system in Oman.

Methods: We combined epidemiological data and whole-genome sequence data from 94 samples of SARS-CoV-2 in Oman to understand the origins, genetic variation, and transmissibility. The whole-genome size of sequence data was obtained through a customized SARS-COV-2 research panel. Amplifier methods ranged from 26 Kbp to 30 Kbp and were submitted to GISAID.

Findings: The study found that P323L (94.7%) is the most common mutation, followed by D614G (92.6%) Spike protein mutation. A unique mutation, I280V, was first reported in Oman and was associated with a rare lineage, B.1.113 (10.6%). In addition, the study revealed a good agreement between genetic and epidemiological data.

Interpretation: Oman's robust surveillance system was very efficient in guiding the outbreak investigation processes in the country, the study illustrates the future importance of molecular epidemiology in leading the national response to outbreaks and pandemics.
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http://dx.doi.org/10.1016/j.ijid.2020.12.049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834852PMC
January 2021

Quinazolinones as Competitive Inhibitors of Carbonic Anhydrase-II (Human and Bovine): Synthesis, , Selectivity, and Kinetics Studies.

Front Chem 2020 1;8:598095. Epub 2020 Dec 1.

Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, Oman.

Carbonic anhydrase-II (CA-II) is associated with glaucoma, malignant brain tumors, and renal, gastric, and pancreatic carcinomas and is mainly involved in the regulation of the bicarbonate concentration in the eyes. CA-II inhibitors can be used to reduce the intraocular pressure usually associated with glaucoma. In search of potent CA-II inhibitors, a series of quinazolinones derivatives () were synthesized and characterized by IR and NMR spectroscopy. The inhibitory potential of all the compounds was evaluated against bovine carbonic anhydrase-II (CA-II) and human carbonic anhydrase-II (CA-II), and compounds displayed moderate to significant inhibition with IC values of 8.9-67.3 and 14.0-59.6 μM, respectively. A preliminary structure-activity relationship suggested that the presence of a nitro group on the phenyl ring at R position contributes significantly to the overall activity. Kinetics studies of the most active inhibitor, , against both CA-II and CA-II were performed to investigate the mode of inhibition and to determine the inhibition constants (Ki). According to the kinetics results, is a competitive inhibitor of CA-II and CA-II with Ki values of 13.0 ± 0.013 and 14.25 ± 0.017 μM, respectively. However, the selectivity index reflects that the compounds and are more selective for CA-II. The binding mode of these compounds within the active sites of CA-II and CA-II was investigated by structure-based molecular docking. The docking results are in complete agreement with the experimental findings.
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http://dx.doi.org/10.3389/fchem.2020.598095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736042PMC
December 2020

Utilization of the common functional groups in bioactive molecules: Exploring dual inhibitory potential and computational analysis of keto esters against α-glucosidase and carbonic anhydrase-II enzymes.

Int J Biol Macromol 2021 Jan 27;167:233-244. Epub 2020 Nov 27.

Department of Chemistry, Faculty of Natural Sciences, The University of Haripur, Haripur, KPK 22620, Pakistan. Electronic address:

Diabetes mellitus, a progressive chronic disease, characterized by the abnormal carbohydrate metabolism is associated with severe health complications including long term dysfunction or failure of several organs, cardiovascular and micro-angiopathic problems (neuropathy, nephropathy, retinopathy). Despite the existence of diverse chemical structural libraries of α-glucosidase inhibitors, the limited diabetic treatment due to the adverse side effects such as abdominal distention, flatulence, diarrhoea, and liver damage associated with these inhibitors encourage the medicinal research community to design and develop new and potent inhibitors of α-glucosidase with better pharmacokinetic properties. In this perspective, we demonstrate the successful integration of common functional groups (ketone & ester) in one combined pharmacophore which is favorable for the formation of hydrogen bonds and other weaker interactions with the target proteins. These keto ester derivatives were screened for their α-glucosidase inhibition potential and the in vitro results revealed compound 3c as the highly active inhibitor with an IC value of 12.4 ± 0.16 μM compared to acarbose (IC = 942 ± 0.74 μM). This inhibition potency was ~76-fold higher than acarbose. Other potent compounds were 3f (IC = 28.0 ± 0.28 μM), 3h (IC = 33.9 ± 0.09 μM), 3g (IC = 34.1 ± 0.04 μM), and 3d (IC = 76.5 ± 2.0 μM). In addition, the emerging use of carbonic anhydrase inhibitors for the treatment of diabetic retinopathy (a leading cause of vision loss) prompted us to screen the keto ester derivatives for the inhibition of carbonic anhydrase-II. Compound 3b was found significantly active against carbonic anhydrase-II with an IC of 16.5 ± 0.92 μM (acetazolamide; IC = 18.2 ± 1.23 μM). Compound 3a also exhibited comparable potency with an IC value of 18.9 ± 1.08 μM. Several structure-activity relationship analyses depicted the influence of the substitution pattern on both the aromatic rings. Molecular docking analysis revealed the formation of several H-bonding interactions through the ester carbonyl and the nitro oxygens of 3c with the side chains of His348, Arg212 and His279 in the active pocket of α-glucosidase whereas 3b interacted with His95, -OH of Thr197, Thr198 and WAT462 in the active site of carbonic anhydrase-II. Furthermore, evaluation of ADME properties suggests the safer pharmacological profile of the tested derivatives.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.11.170DOI Listing
January 2021

Involvement of selective GABA-A receptor subtypes in amelioration of cisplatin-induced neuropathic pain by 2'-chloro-6-methyl flavone (2'-Cl-6MF).

Naunyn Schmiedebergs Arch Pharmacol 2020 Nov 22. Epub 2020 Nov 22.

Natural and Medical Sciences Research Center, University of Nizwa, Birkat Al Mauz, 616, Nizwa, Oman.

Cisplatin-induced peripheral neuropathic pain is a common adverse effect of chemotherapy. The present study evaluated the effects of 2'-chloro-6-methylflavone (2'-Cl-6MF) at recombinant α1β2γ2L, α2β1-3γ2L, and α3β1-3γ2L GABA-A receptor subtypes expressed in Xenopus oocytes and subsequently evaluated its effectiveness in cisplatin-induced neuropathic pain. The results showed that 2'-Cl-6MF potentiated GABA-elicited currents at α2β2/3γ2L and α3β2/3γ2L GABA-A receptor subtypes. The potentiation was blocked by the co-application of flumazenil (a benzodiazepine (BDZs) site antagonist). In behavioral studies, mechanical allodynia was induced by intraplantar injection of cisplatin (40 μg/paw) in Sprague Dawley rats, and behavioral assessments were made 24 h after injection. 2'-Cl-6MF (1, 10, 30, and 100 mg/kg, i.p.), was administered 1 h before behavioral evaluation. Administration of 2'-Cl-6MF (30 and 100 mg/kg, i.p) significantly enhanced the paw withdrawal threshold and decreased mechanical allodynia. The standard drugs, gabapentin (GBP) at the dose of 70 mg/kg, and HZ 166 (16 mg/kg), i.p. also significantly enhanced the paw withdrawal threshold in mechanical allodynia. Pretreatment with pentylenetetrazole (PTZ) (15 mg/kg, i.p.) and flumazenil reversed the antinociceptive effect of 2'-Cl-6MF in mechanical allodynia indicating GABAergic mechanisms. Moreover, the binding mechanism of 2'-Cl-6MF was rationalized by in silico modeling tools. The 3D-coordinates of α2β2γ2L and α2β3γ2L were generated after homology modeling of the α2 subtype and 2'-Cl-6MF was at predicted binding sites of the developed models. The α2 model was compared with the α1 and α3 subunits via structural and sequence alignment. Molecular docking depicted that the compound binds efficiently at the neuromodulator binding site of the receptors. The findings of this study revealed that 2'-Cl-6MF ameliorated the manifestations of cisplatin-induced neuropathic pain in rats. Furthermore, we also conclude that GABAergic mechanisms may contribute to the antinociceptive effect of 2'-Cl-6MF. The molecular docking studies also confirm the involvement of the BDZs site of GABA-A receptors. It was observed that Ile230 of α2 stabilize the chlorophenyl ring of 2'-Cl-6MF through hydrophobic interactions, which is replaced by Val203 in α1 subunit. However, the smaller side chain of Val203 does not provide hydrophobic interaction to the compound due to high conformational flexibility of α1 subunit.
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http://dx.doi.org/10.1007/s00210-020-02021-xDOI Listing
November 2020

Construction of anti-codon table of the plant kingdom and evolution of tRNA selenocysteine (tRNA).

BMC Genomics 2020 Nov 19;21(1):804. Epub 2020 Nov 19.

Natural and Medical Sciences Research Center, University of Nizwa, 616, Nizwa, Oman.

Background: The tRNAs act as a bridge between the coding mRNA and incoming amino acids during protein translation. The anti-codon of tRNA recognizes the codon of the mRNA and deliver the amino acid into the protein translation chain. However, we did not know about the exact abundance of anti-codons in the genome and whether the frequency of abundance remains same across the plant lineage or not.

Results: Therefore, we analysed the tRNAnome of 128 plant species and reported an anti-codon table of the plant kingdom. We found that CAU anti-codon of tRNA has highest (5.039%) whereas GCG anti-codon of tRNA has lowest (0.004%) abundance. However, when we compared the anti-codon frequencies according to the tRNA isotypes, we found tRNA (7.808%) has highest abundance followed by tRNA (7.668%) and tRNA (7.523%). Similarly, suppressor tRNA (0.036%) has lowest abundance followed by tRNA (0.066%) and tRNA (2.109). The genome of Ipomoea nil, Papaver somniferum, and Zea mays encoded the highest number of anti-codons (isoacceptor) at 59 each whereas the genome of Ostreococcus tauri was found to encode only 18 isoacceptors. The tRNA genes undergone losses more frequently than duplication and we found that tRNA showed anti-codon switch during the course of evolution.

Conclusion: The anti-codon table of the plant tRNA will enable us to understand the synonymous codon usage of the plant kingdom and can be very helpful to understand which codon is preferred over other during the translation.
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http://dx.doi.org/10.1186/s12864-020-07216-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678280PMC
November 2020

Gene Loss and Evolution of the Plastome.

Genes (Basel) 2020 Sep 25;11(10). Epub 2020 Sep 25.

Natural Product Laboratory, Natural and Medical Sciences Research Centre, University of Nizwa, Nizwa 616, Oman.

Chloroplasts are unique organelles within the plant cells and are responsible for sustaining life forms on the earth due to their ability to conduct photosynthesis. Multiple functional genes within the chloroplast are responsible for a variety of metabolic processes that occur in the chloroplast. Considering its fundamental role in sustaining life on the earth, it is important to identify the level of diversity present in the chloroplast genome, what genes and genomic content have been lost, what genes have been transferred to the nuclear genome, duplication events, and the overall origin and evolution of the chloroplast genome. Our analysis of 2511 chloroplast genomes indicated that the genome size and number of coding DNA sequences (CDS) in the chloroplasts genome of algae are higher relative to other lineages. Approximately 10.31% of the examined species have lost the inverted repeats (IR) in the chloroplast genome that span across all the lineages. Genome-wide analyses revealed the loss of the gene in parasitic and heterotrophic plants occurred approximately 56 Ma ago. and were found to be characteristic signature genes of the chloroplast genome of algae, bryophytes, pteridophytes, and gymnosperms; however, none of these genes were found in the angiosperm or magnoliid lineage which appeared to have lost them approximately 203-156 Ma ago. A variety of chloroplast-encoded genes were lost across different species lineages throughout the evolutionary process. The gene, however, was found to be the most stable and intact gene in the chloroplast genome and was not lost in any of the analyzed species, suggesting that it is a signature gene of the plastome. Our evolutionary analysis indicated that chloroplast genomes evolved from multiple common ancestors ~1293 Ma ago and have undergone vivid recombination events across different taxonomic lineages.
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http://dx.doi.org/10.3390/genes11101133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650654PMC
September 2020

VD and LXR agonist (T0901317) combination demonstrated greater potency in inhibiting cholesterol accumulation and inducing apoptosis via ABCA1-CHOP-BCL-2 cascade in MCF-7 breast cancer cells.

Mol Biol Rep 2020 Oct 29;47(10):7771-7782. Epub 2020 Sep 29.

Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, Sultanate of Oman.

Obesity is associated with hypercholesterolemia and is a global epidemic. Epidemiological and animal studies revealed cholesterol is an essential regulator of estrogen receptor positive (ER+) breast cancer progression while inhibition of cholesterol accumulation was found to prevent breast tumor growth. Individually, vitamin D and LXR agonist T0901317 showed anticancer properties. The present study investigated the effects of vitamin D (VD, calcitriol), LXR agonist (T0901317) and a combination of VD + T0901317 on cholesterol metabolism and cancer progression in ER+ breast cancer (MCF-7) cells. VD or T0901317 alone reduced cholesterol accumulation significantly in MCF-7 cells concomitant with an induction of ABCA1 protein and gene expression compared to the control treatment. Most importantly, VD + T0901317 combination showed higher effects in reducing cholesterol levels and increasing ABCA1 protein and gene expression compared to individual treatments. Importantly, VD + T0901317 combination showed higher effects in increasing apoptosis as measured by annexin apoptosis assay, cell viability and was associated with induction of CHOP protein and gene expression. Additionally, the VD + T0901317 exerted higher effects in reducing antiapoptotic BCL-2 while increased pro-apoptotic BAX gene expression compared to the individual treatments. The present results suggest that VD and T0901317 combination may have an important therapeutic application to prevent obesity and hyperlipidemia mediated ER+ breast cancer progression.
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http://dx.doi.org/10.1007/s11033-020-05854-0DOI Listing
October 2020

Synthesis of Spiro-β-lactam-pyrroloquinolines as Fused Heterocyclic Scaffolds through Post-transformation Reactions.

J Org Chem 2020 10 28;85(20):13141-13152. Epub 2020 Sep 28.

Natural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, Birkat Al Mauz, 616 Nizwa, Sultanate of Oman.

A sequential post-transformation of Ugi four-component reaction/nucleophilic substitution was developed for the synthesis of spiro-β-lactam-pyrroloquinolines. This method involves the Ugi-4CR of 2-chloro-3-formyl quinolines -, amines -, 2-chloroacetic acid , and isocyanides , for the synthesis of versatile precursors -. The Ugi adducts were intramolecularly cyclized under basic conditions through the sequential nucleophilic aromatic substitution (SAr)/second-order nucleophilic substitution (S2) reaction to give spiro-β-lactam-pyrroloquinoline scaffolds -. This approach is an efficient method for the synthesis of fused bioactive heterocyclic backbones containing quinoline, pyrrolidone, and β-lactam with high bond-forming efficiency.
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http://dx.doi.org/10.1021/acs.joc.0c01817DOI Listing
October 2020

Global Trends in Phytohormone Research: Google Trends Analysis Revealed African Countries Have Higher Demand for Phytohormone Information.

Plants (Basel) 2020 Sep 22;9(9). Epub 2020 Sep 22.

Natural and Medical Sciences Research Center, University of Nizwa, Nizwa 616, Oman.

The lines of research conducted within a country often reflect its focus on current and future economic needs. Analyzing "search" trends on the internet can provide important insight into predicting the direction of a country in regards to agriculture, health, economy, and other areas. 'Google Trends' collects data on search terms from different countries, and this information can be used to better understand sentiments in different countries and regions. Agricultural output is responsible for feeding the world and there is a continuous quest to find ways to make agriculture more productive, safe, and reliable. The application of phytohormones has been used in agriculture world-wide for many years to improve crop production and continues to be an active area of research for the application in plants. Therefore, in the current study, we searched 'Google Trends' using the phytohormone search terms, abscisic acid, auxins, brassinosteroids, cytokinin, ethylene, gibberellins, jasmonic acid, salicylic acid, and strigolactones. The results indicated that the African country Zambia had the greatest number of queries on auxin research, and Kenya had the most queries in cytokinin and gibberellin research world-wide. For other phytohormones, India had the greatest number of queries for abscisic acid and South Korea had the greatest number of ethylene and jasmonic acid search world-wide. Queries on salicylic acid have been continuously increasing while the least number of queries were related to strigolactones. Only India and United States of America had significant numbers of queries on all nine phytohormones while queries on one or more phytohormones were absent in other countries. India is one of the top five crop-producing countries in the world for apples, millet, orange, potato, pulses, rice, sugarcane, tea, and wheat. Similarly, the United States of America is one of the top five crop-producing countries of the world for apples, grapes, maze, orange, potato, sorghum, sugarcane, and wheat. These might be the most possible factors for the search queries found for all the nine phytohormones in India and the United States of America.
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http://dx.doi.org/10.3390/plants9091248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570059PMC
September 2020

New multitarget directed benzimidazole-2-thiol-based heterocycles as prospective anti-radical and anti-Alzheimer's agents.

Drug Dev Res 2020 Sep 8. Epub 2020 Sep 8.

Department of Chemistry, University of Malakand, Chakdara, Khyber Pakhtunkhwa, Pakistan.

A series of new heterocycles (4-18) was synthesized by the structural modification of benzimidazole-2-thiol (BT, 2-MBI). The structures of the synthesized compounds were confirmed with the help of high-resolution mass spectrometry (HRMS) and HNMR spectroscopy. High inhibitions of the oxidants such as ABTS and DPPH were observed for compounds 9 [IC (s) = 167.4 μM (ABTS), 139.5 μM (DPPH)], 10 [IC (s) = 186.5 μM (ABTS), 155.4 μM (DPPH)], 11 [IC (s) = 286.1 μM (ABTS), 189.1 μM (DPPH)], 12 [IC (s) = 310.8 μM (ABTS), 162.2 μM (DPPH)], 14 [IC (s) = 281.3 μM (ABTS), 205.7 μM (DPPH)], 15 [IC (s) = 284.1 μM (ABTS), 177.3 μM (DPPH)], and 16 [IC (s) = 344.7 μM (ABTS), 270.2 μM (DPPH)] as compared with Ascorbic acid [IC (s) = 340.9 μM (ABTS), 164.3 μM (DPPH)]. The anti-Alzheimer's activity was performed in vitro against cholinesterase enzymes (AChE, BChE). Compound 11 was able to show significant inhibitions [IC (s) = 121.2 μM (AChE), 38.3 μM (BChE)] as against that of galantamine [IC (s) = 139.4 μM (AChE), 40.3 μM (BChE)]. Compound 14 was found as a very good inhibitor of butyrylcholinesterase (IC = 35.4 μM) as compared with standard galantamine. Molecular docking was further performed to investigate the mechanism of anticholinesterase activity.
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http://dx.doi.org/10.1002/ddr.21740DOI Listing
September 2020

An Aminopyridinium Ionic Liquid: A Simple and Effective Bifunctional Organocatalyst for Carbonate Synthesis from Carbon Dioxide and Epoxides.

Chempluschem 2020 07;85(7):1587-1595

Natural and Medical Sciences Research Center (NMSRC), University of Nizwa, 616, Nizwa, Sultanate of Oman.

An aminopyridinium ionic liquid is presented as a green, tunable, and active metal-free one-component catalytic system for the atom-efficient transformation of oxiranes and CO to cyclic carbonates. Inclusion of a positively charged moiety into aminopyridines, through a simple single-step synthesis, provides a one-component ionic liquid catalytic system with superior activity; effective in ring opening of epoxide, CO inclusion, and stabilization of oxoanionic intermediates. An efficiency assessment of a variety of positively charged aminopyridines was pursued, and the impact of temperature, catalyst loading, and the kind of nucleophile on the catalytic performance was also investigated. Under solvent-free conditions, this bifunctional organocatalytic system was used for the preparation of 18 examples of cyclic carbonates from a broad range of alkyl- and aryl-substituted oxiranes and CO , where up to 98 % yield and high selectivity were achieved. DFT calculations validated a mechanism in which nucleophilic ring-opening and CO inclusion occur simultaneously towards cyclic carbonate formation.
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http://dx.doi.org/10.1002/cplu.202000367DOI Listing
July 2020

In silico data mining of large-scale databases for the virtual screening of human interleukin-2 inhibitors.

Acta Pharm 2021 Mar;71(1):33-56

Natural and Medical Science Research Center, University of Nizwa Birkat-ul-Mouz 616, Nizwa Sultanate of Oman.

Interleukin-2 (IL-2) is involved in the activation and differentiation of T-helper cells. Uncontrolled activated T cells play a key role in the pathophysiology by stimulating inflammation and autoimmune diseases like arthritis, psoriasis and Crohn's disease. T cells activation can be suppressed either by preventing IL-2 production or blocking the IL-2 interaction with its receptor. Hence, IL-2 is now emerging as a target for novel therapeutic approaches in several autoimmune disorders. This study was carried out to set up an effective virtual screening (VS) pipeline for IL-2. Four docking/scoring approaches (FRED, MOE, GOLD and Surflex-Dock) were compared in the re-docking process to test their performance in producing correct binding modes of IL-2 inhibitors. Surflex-Dock and FRED were the best in predicting the native pose in its top-ranking position. Shapegauss and CGO scoring functions identified the known inhibitors of IL-2 in top 1, 5 and 10 % of library and differentiated binders from non-binders efficiently with average AUC of > 0.9 and > 0.7, resp. The applied docking protocol served as a basis for the VS of a large database that will lead to the identification of more active compounds against IL-2.
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http://dx.doi.org/10.2478/acph-2021-0002DOI Listing
March 2021

Diterpenoids and Triterpenoids From Frankincense Are Excellent Anti-psoriatic Agents: An Approach.

Front Chem 2020 25;8:486. Epub 2020 Jun 25.

Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, Oman.

Psoriasis is a chronic autoimmune disease that affects 2-3% of the global population and requires an effective treatment. Frankincense has been long known for its potent anti-inflammatory activities. In this study, a structural bioinformatics approach was used to evaluate the efficacy of individual active components of frankincense, macrocyclic diterpenoid derivatives (-), and boswellic acids (-) in the treatment of psoriasis. Initially, major druggable targets of psoriasis were identified. Subsequently, structure-based screening was employed by using three different docking algorithms and scoring functions (MOE, AutoDock Vina, and MVD) for the target fishing of compounds against 18 possible targets of psoriasis. Janus Kinase 1, 2, 3 (JAK 1/2/3), eNOS, iNOS, interleukin-17 (IL-17), and Tumor necrosis factor-α (TNF-α) were identified as the preferred molecular targets for these compounds. This computational analysis reflects that frankincense diterpenoids and triterpenoids can serve as excellent anti-psoriatic agents by targeting major cytokines (TNF-α, IL-17, IL-13, IL-23, and IL-36γ,) exacerbated in psoriasis, and inflammatory pathways particularly JAK1/2/3, eNOS, iNOS, MAPK2, and IFNγ. The results were compared with the reported experimental findings which correlates well with our verdicts.
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http://dx.doi.org/10.3389/fchem.2020.00486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330179PMC
June 2020

Transcriptomic analysis of Dubas bug (Ommatissus lybicus Bergevin) infestation to Date Palm.

Sci Rep 2020 07 13;10(1):11505. Epub 2020 Jul 13.

Natural and Medical Sciences Research Center, University of Nizwa, 616, Nizwa, Oman.

Date palm (Phoenix dactylifera L.) and its fruit possess sociocultural, health and economic importance in Middle East. The date palm plantations are prone to Dubas bug (DB; Ommatissus lybicus DeBergevin; Homoptera: Tropiduchidae) attacks that severely damages the tree's growth and reduces fruit production. However, the transcriptome related datasets are not known to understand how DB activates physiological and gene regulatory mechanisms during infestation. Hence, we performed RNA-Seq of leaf infected with or without DB to understand the molecular responses of date palm seedlings. Before doing that, we noticed that DB infestation significantly increase superoxide anion and malondialdehyde production to two-folds as compared to healthy control. Stress-responsive genes such as proline transporter 2, NADP-dependent glyceraldehyde and superoxide dismutase were found significantly upregulated in infected seedlings. The infection repercussions were also revealed by significantly higher contents of endogenous phytohormonal signaling of jasmonic acid (JA) and salicylic acid (SA) compared with control. These findings persuaded to dig out intrinsic mechanisms and gene regulatory networks behind DB infestation to date palm by RNA-Seq analysis. Transcriptome analysis revealed upregulation of 6,919 genes and down-regulation of 2,695 genes in leaf during the infection process. The differentially expressed genes were mostly belongs to cellular functions (calcium and MAPK), phytohormones (auxin, gibberellins, abscisic acid, JA and SA), and secondary metabolites (especially coumarinates and gossypol). The data showed that defense responses were aggravated by gene networks involved in hypersensitive responses (PAR1, RIN4, PBS1 etc.). In conclusion, the results revealed that date palm's leaf up-regulates both cellular and phytohormonal determinants, followed by intrinsic hypersensitive responses to counter infestation process by Dubas bug.
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http://dx.doi.org/10.1038/s41598-020-67438-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359322PMC
July 2020

Heterogeneous Pd/C-catalyzed, ligand free Suzuki-Miyaura coupling reaction furnishes new -terphenyl derivatives.

Nat Prod Res 2020 Jul 13:1-5. Epub 2020 Jul 13.

Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, Oman.

A series of new -terphenyls derivatives have been efficiently synthesized by a ligand-free heterogeneous Pd/C-catalyzed two-fold Suzuki-Miyaura coupling reaction. Methyl 5-bromo-2-iodobenzoate was selected to react with a variety of different aryl boronic acids (). Nine new -terphenyl derivatives (-) were prepared and the structures were confirmed by several analytical techniques including infrared, spectroscopy, H and C NMR spectroscopy, mass spectrometry, and in the case of compound by X-ray diffraction method. The new derivatives were obtained in very good yields (78-91%). This synthetic facile route is envisioned to improve the preparation of -terphenyl-based natural products.
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http://dx.doi.org/10.1080/14786419.2020.1791112DOI Listing
July 2020

Secondary metabolites from acridocarpus orientalis inhibits 4T1 cells and promotes mesenchymal stem cells (MSCs) proliferation.

Mol Biol Rep 2020 Jul 4;47(7):5421-5430. Epub 2020 Jul 4.

Laboratory for Stem Cell & Regenerative Medicine, Natural and Medical Sciences Research Center, University of Nizwa, P. O. Box: 33, Nizwa, PC, 616, Oman.

Among medicinal plants, Acridocarpus orientalis (AO) possesses a remarkable anti-cancer potential, possibly because of its anti-oxidant property. In this study, the leaf and stem extracts from AO were assessed to find the bioactive compound with selective anti-cancer properties. The MTT viability and live and dead assays revealed that around 80% and 98% of 4T1 cells survival were declined after 48 h incubation with leaf and stem extracts, respectively. The leaf extract increased stem cell proliferation by 20% whereas the stem extract inhibited around 22% of stem cells proliferation after 48 h treatment. The live and dead assay of MSCs confirmed that 40% of the MSCs died when treated with AO stem extract. On the other hand, there were no dead cells after two days of treatment with the leaf extract. Followed by the induction of cell cycle arrest in G0/G1-phase, the real-time PCR demonstrated apoptosis properties in 4T1 cells through overexpression of Bax and down-regulation of BCL2 genes. Interestingly, within the pure compounds isolated from AO leaf extract, Morin was responsible for the inhibition of 4T1 cells proliferation as well as MSCs expansion, predicting to play an essential role in the treatment of cancer. The promising in vitro anti-cancer and stem cell-inductive properties of morin isolated from AO extract may provide a great potential to produce selective herbal derived drugs.
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http://dx.doi.org/10.1007/s11033-020-05632-yDOI Listing
July 2020

FT-NIRS Coupled with PLS Regression as a Complement to HPLC Routine Analysis of Caffeine in Tea Samples.

Foods 2020 Jun 24;9(6). Epub 2020 Jun 24.

Department of Biological Sciences & Chemistry, College of Arts and Sciences, University of Nizwa, P.O. Box 33, Nizwa 611, Oman.

Daily consumption of caffeine in coffee, tea, chocolate, cocoa, and soft drinks has gained wide and plentiful public and scientific attention over the past few decades. The concentration of caffeine in vivo is a crucial indicator of some disorders-for example, kidney malfunction, heart disease, increase of blood pressure and alertness-and can cause some severe diseases including type 2 diabetes mellitus (DM), stroke risk, liver disease, and some cancers. In the present study, near-infrared spectroscopy (NIRS) coupled with partial least-squares regression (PLSR) was proposed as an alternative method for the quantification of caffeine in 25 commercially available tea samples consumed in Oman. This method is a fast, complementary technique to wet chemistry procedures as well as to high-performance liquid chromatography (HPLC) methods for the quantitative analysis of caffeine in tea samples because it is reagent-less and needs little or no pre-treatment of samples. In the current study, the partial least-squares (PLS) algorithm was built by using the near-infrared NIR spectra of caffeine standards prepared in tea samples scanned by a Frontier NIR spectrophotometer (L1280034) by PerkinElmer. Spectra were collected in the absorption mode in the wavenumber range of 10,000-4000 cm, using a 0.2 mm path length and CaF sealed cells with a resolution of 2 cm. The NIR results for the contents of caffeine in tea samples were also compared with results obtained by HPLC analysis. Both techniques provided good results for predicting the caffeine contents in commercially available tea samples. The results of the proposed study show that the suggested FT-NIRS coupled with PLS regression algorithun has a high potential to be routinely used for the quick and reproducible analysis of caffeine contents in tea samples. For the NIR method, the limit of quantification (LOQ) was estimated as 10 times the error of calibration (root mean square error of calibration (RMSECV)) of the model; thus, RMSEC was calculated as 0.03 ppm and the LOQ as 0.3 ppm.
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http://dx.doi.org/10.3390/foods9060827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353657PMC
June 2020

Silicon-induced thermotolerance in Solanum lycopersicum L. via activation of antioxidant system, heat shock proteins, and endogenous phytohormones.

BMC Plant Biol 2020 Jun 3;20(1):248. Epub 2020 Jun 3.

School of Applied Biosciences, Kyungpook National University, Daegu, 41566, South Korea.

Background: Abiotic stresses (e.g., heat or limited water and nutrient availability) limit crop production worldwide. With the progression of climate change, the severity and variation of these stresses are expected to increase. Exogenous silicon (Si) has shown beneficial effects on plant growth; however, its role in combating the negative effects of heat stress and their underlying molecular dynamics are not fully understood.

Results: Exogenous Si significantly mitigated the adverse impact of heat stress by improving tomato plant biomass, photosynthetic pigments, and relative water content. Si induced stress tolerance by decreasing the concentrations of superoxide anions and malondialdehyde, as well as mitigating oxidative stress by increasing the gene expression for antioxidant enzymes (peroxidases, catalases, ascorbate peroxidases, superoxide dismutases, and glutathione reductases) under stress conditions. This was attributed to increased Si uptake in the shoots via the upregulation of low silicon (SlLsi1 and SlLsi2) gene expression under heat stress. Interestingly, Si stimulated the expression and transcript accumulation of heat shock proteins by upregulating heat transcription factors (Hsfs) such as SlHsfA1a-b, SlHsfA2-A3, and SlHsfA7 in tomato plants under heat stress. On the other hand, defense and stress signaling-related endogenous phytohormones (salicylic acid [SA]/abscisic acid [ABA]) exhibited a decrease in their concentration and biosynthesis following Si application. Additionally, the mRNA and gene expression levels for SA (SlR1b1, SlPR-P2, SlICS, and SlPAL) and ABA (SlNCEDI) were downregulated after exposure to stress conditions.

Conclusion: Si treatment resulted in greater tolerance to abiotic stress conditions, exhibiting higher plant growth dynamics and molecular physiology by regulating the antioxidant defense system, SA/ABA signaling, and Hsfs during heat stress.
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http://dx.doi.org/10.1186/s12870-020-02456-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268409PMC
June 2020

Synthesis and Modeling Studies of Furoxan Coupled Spiro-Isoquinolino Piperidine Derivatives as NO Releasing PDE 5 Inhibitors.

Biomedicines 2020 May 14;8(5). Epub 2020 May 14.

School of Chemical Sciences, SRTM University, Nanded 431606, Maharashtra, India.

Nitric oxide (NO) is considered to be one of the most important intracellular messengers that play an active role as neurotransmitter in regulation of various cardiovascular physiological and pathological processes. Nitric oxide (NO) is a major factor in penile erectile function. NO exerts a relaxing action on corpus cavernosum and penile arteries by activating smooth muscle soluble guanylate cyclase and increasing the intracellular concentration of cyclic guanosine monophosphate (cGMP). Phophodiesterase (PDE) inhibitors have potential therapeutic applications. NO hybridization has been found to improve and extend the pharmacological properties of the parental compound. The present study describes the synthesis of novel furoxan coupled spiro-isoquinolino-piperidine derivatives and their smooth muscle relaxant activity. The study reveals that, particularly (1.50 ± 0.6) and (1.65 ± 0.7) are moderate PDE 5 inhibitors as compared to Sidenafil (1.43 ± 0.5). The observed effect was explained by molecular modelling studies on phosphodiesterase.
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http://dx.doi.org/10.3390/biomedicines8050121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277557PMC
May 2020

In Silico Modeling of Crimean Congo Hemorrhagic Fever Virus Glycoprotein-N and Screening of Anti Viral Hits by Virtual Screening.

Int J Pept Res Ther 2020 Mar 11:1-14. Epub 2020 Mar 11.

1Natural and Medical Sciences Research Center, University of Nizwa, Birkat Al Mauz, Nizwa, Sultanate of Oman.

Crimean-Congo hemorrhagic fever (CCHF) is a widespread zoonotic viral disease, caused by a tick-born virus Crimean-Congo hemorrhagic fever virus (CCHFV). This disease is endemic in Middle East, Asia, Africa and South-Eastern Europe with the mortality rate of 5-30%. CCHFV genome is composed of three segments: large, medium and small segments. M segment encodes a polyprotein (glycoprotein) so called glycoprotein N (Gn) which is considered as a potential druggable target for the effective therapy of CCHF. The complete structure of Gn is still not characterized. The aim of the current study is to predict the complete three-dimensional (3D-) structure of CCHFV Gn protein via threading-based modeling and investigate the residues crucial for binding with CCHFV envelop. The developed model displayed excellent stereo-chemical and geometrical properties. Subsequently structure based virtual screening (SBVS) was applied to discover novel inhibitors of Gn protein. A library of > 1300 anti-virals was selected from PubChem database and directed to the predicted binding site of Gn. The SBVS results led to the identification of thirty-seven compounds that inhibit the protein in computational analysis. Those 37 hits were subject to pharmacokinetic profiling which demonstrated that 30/37 compound possess safer pharmacokinetic properties. Thus, by specifically targeting Gn, less toxic and more potent inhibitors of CCHFV were identified in silico.
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http://dx.doi.org/10.1007/s10989-020-10055-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223756PMC
March 2020

Antiproliferative and Carbonic Anhydrase II Inhibitory Potential of Chemical Constituents from and : Evidence from In Silico Target Fishing and In Vitro Testing.

Pharmaceuticals (Basel) 2020 May 13;13(5). Epub 2020 May 13.

Natural & Medical Sciences Research Center, University of Nizwa, P.O Box 33, 616 Birkat Al Mauz, Nizwa, Sultanate of Oman.

Roem. & Schult and resin of (L.) BURM. F. are commonly used in Omani traditional medication against various ailments. Herein, their antiproliferative and antioxidant potential was explored. Bioassay-guided fractionation of the methanol extract of both plants led to the isolation of 14 known compounds, viz., - from and - from Their structures were confirmed by combined spectroscopic techniques including 1D (H and C) and 2D (HMBC, HSQC, COSY) nuclear magnetic resonance (NMR), and electrospray ionization-mass spectrometry (ESI-MS). The cytotoxic potential of isolates was tested against the triple-negative breast cancer cell line (MDA-MB-231). Compound exhibited excellent antiproliferative activity in a range of 31 μM, followed by compounds -, , and , which depicted IC values in the range of 35-60 μM, while , , and also demonstrated IC values >72 μM. Subsequently, in silico target fishing was applied to predict the most potential cellular drug targets of the active compounds, using pharmacophore modeling and inverse molecular docking approach. The extensive in silico analysis suggests that our compounds may target carbonic anhydrase II (CA-II) to exert their anticancer activities. When tested on CA-II, compounds (IC = 14.4 µM), (IC = 23.3), and (IC = 24.4 µM) showed excellent biological activities in vitro. Additionally, the ethyl acetate fraction of both plants showed promising antioxidant activity. Among the isolated compounds, possesses the highest antioxidant (55 μM) activity followed by (241 μM). The results indicated that compound can be a promising candidate for antioxidant drugs, while compound is a potential candidate for anticancer drugs.
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http://dx.doi.org/10.3390/ph13050094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281707PMC
May 2020