Publications by authors named "Kalavathy Ramasamy"

88 Publications

Multidomain Intervention for Reversal of Cognitive Frailty: Towards a Personalized Approach (AGELESS Trial): Study Design.

J Alzheimers Dis 2021 Jun 3. Epub 2021 Jun 3.

Division of Clinical Geriatrics, Karolinska Institutet, Solna, Sweden.

Background: Cognitive frailty (CF) is identified as one of the main precursors of dementia. Multidomain intervention has been found to delay or prevent the onset of CF.

Objective: The aim of our present study is to determine the effectiveness of a comprehensive, multidomain intervention on CF; to evaluate its cost effectiveness and the factors influencing adherence toward this intensive intervention.

Methods: A total of 1,000 community dwelling older adults, aged 60 years and above will be screened for CF. This randomized controlled trial involves recruitment of 327 older adults with CF from urban, semi-urban, and rural areas in Malaysia. Multidomain intervention comprised of physical, nutritional, cognitive, and psychosocial aspects will be provided to participants in the experimental group (n = 164). The control group (n = 164) will continue their usual care with their physician. Primary outcomes include CF status, physical function, psychosocial and nutritional status as well as cognitive performance. Vascular health and gut microbiome will be assessed using blood and stool samples. A 24-month intensive intervention will be prescribed to the participants and its sustainability will be assessed for the following 12 months. The effective intervention strategies will be integrated as a personalized telerehabilitation package for the reversal of CF for future use.

Results: The multidomain intervention developed from this trial is expected to be cost effective compared to usual care as well as able to reverse CF.

Conclusion: This project will be part of the World-Wide FINGERS (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability) Network, of which common identifiable data will be shared and harmonized among the consortia.
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http://dx.doi.org/10.3233/JAD-201607DOI Listing
June 2021

Virgin Coconut Oil-Induced Neuroprotection in Lipopolysaccharide-Challenged Rats is Mediated, in Part, Through Cholinergic, Anti-Oxidative and Anti-Inflammatory Pathways.

J Diet Suppl 2020 Oct 14:1-27. Epub 2020 Oct 14.

Collaborative Drug Discovery Research (CDDR) Group, Faculty of Pharmacy, Universiti Teknologi MARA (UiTM) Cawangan Selangor, Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.

Neuroinflammation is associated with neuronal cell death and could lead to chronic neurodegeneration. This study investigated the neuroprotective potential of virgin coconut oil (VCO) against lipopolysaccharide (LPS)-induced cytotoxicity of neuroblastoma SK-N-SH cells. The findings were validated using Wistar rats, which were fed with 1-10 g/kg VCO for 31 days, exposed to LPS (0.25 mg/kg) and subjected to the Morris Water Maze Test. Brain homogenate was subjected to biochemical analyses and gene expression studies. α-Tocopherol (α-T; 150 mg/kg) served as the positive control. VCO (100 µg/mL) significantly ( < 0.01) improved SK-N-SH viability (+57%) and inhibited reactive oxygen species (-31%) in the presence of LPS. VCO (especially 10 g/kg) also significantly ( < 0.05) enhanced spatial memory of LPS-challenged rats. Brain homogenate of VCO-fed rats was presented with increased acetylcholine (+33%) and reduced acetylcholinesterase (-43%). The upregulated antioxidants may have reduced neuroinflammation [malondialdehyde (-51%), nitric oxide (-49%), (-64%) and (-63%)] through upregulation of IL-10 (+30%) and downregulation of IL-1β (-65%) and Interferon-γ (-25%). There was also reduced expression of (-77%). VCO-induced neuroprotection, which was comparable to α-T, could be mediated, in part, through inflammatory, cholinergic and amyloidogenic pathways.
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http://dx.doi.org/10.1080/19390211.2020.1830223DOI Listing
October 2020

Differential gut microbiota composition between type 2 diabetes mellitus patients and healthy controls: A systematic review.

Diabetes Res Clin Pract 2021 Mar 4;173:108689. Epub 2021 Feb 4.

Collaborative Drug Discovery Research (CDDR) Group, Faculty of Pharmacy, Universiti Teknologi MARA (UiTM) Kampus Puncak Alam, Cawangan Selangor, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.

Aims: This systematic review summarised the latest findings on differential composition of gut microbiota in T2DM.

Methods: Literature search was performed using electronic databases. Relevant studies were identified, extracted and assessed for risk of bias. The primary outcome of this systematic review was the composition of gut microbiota in healthy controls and T2DM while the secondary outcomes included the correlation of gut microbiota with metabolic parameters.

Results: Thirteen case-control studies involving 575 T2DM and 840 healthy controls were included. T2DM patients exhibited a marked increase in lactobacilli. Six studies found lactobacilli to predominate the gut of T2DM patients; however, this could be confounded by the types of antihyperglyacemic medications. Conversely, butyrate producers dominate the gut of healthy controls. In T2DM patients, butyrate producers were surprisingly higher in those taking metformin intake than those not taking the drug. Whilst lactobacilli were found to be higher with increased plasma glucose, conflicting correlations were observed between various genera and anthropometric measurements, dietary intake, lipid profiles and inflammatory markers. There were moderate to strong significant positive correlations between the class Clostridia and phylum Firmicutes with pro-inflammatory IFN-γ as well as between Negativicutes and IL-6.

Conclusions: Altogether, butyrate-producing bacteria are negatively correlated to glycaemic parameters. Lactobacilli are higher in T2DM patients and Firmicutes is correlated with inflammation.
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http://dx.doi.org/10.1016/j.diabres.2021.108689DOI Listing
March 2021

Synthesis and biological evaluation of heterocyclic 1,2,4-triazole scaffolds as promising pharmacological agents.

BMC Chem 2021 Jan 21;15(1). Epub 2021 Jan 21.

Faculty of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, 124001, India.

Background: Triazole is an important heterocyclic moiety that occupies a unique position in heterocyclic chemistry, due to its large number of biological activities. It exists in two isomeric forms i.e. 1,2,4-triazole and 1,2,3-triazole and is used as core molecule for the design and synthesis of many medicinal compounds. 1,2,4-Triazole possess broad spectrum of therapeutically interesting drug candidates such as analgesic, antiseptic, antimicrobial, antioxidant, anti-urease, anti-inflammatory, diuretics, anticancer, anticonvulsant, antidiabetic and antimigraine agents.

Methods: The structures of all synthesized compounds were characterized by physicochemical properties and spectral means (IR and NMR). The synthesized compounds were evaluated for their in vitro antimicrobial activity against Gram-positive (B. subtilis), Gram-negative (P. aeruginosa and E. coli) bacterial and fungal (C. albicans and A. niger) strains by tube dilution method using ciprofloxacin, amoxicillin and fluconazole as standards. In-vitro antioxidant and anti-urease screening was done by DPPH assay and indophenol method, respectively. The in-vitro anticancer evaluation was carried out against MCF-7 and HCT116 cancer cell lines using 5-FU as standards.

Results, Discussion And Conclusion: The biological screening results reveal that the compounds T (MIC = 24.7 µM, MIC,  = 12.3 µM) and T (MIC = 27.1 µM) exhibited potent antimicrobial activity as comparable to standards ciprofloxacin, amoxicillin (MIC = 18.1 µM, MIC = 17.1 µM) and fluconazole (MIC = 20.4 µM), respectively. The antioxidant evaluation showed that compounds T (IC = 34.83 µg/ml) and T (IC = 34.38 µg/ml) showed significant antioxidant activity and comparable to ascorbic acid (IC = 35.44 µg/ml). Compounds T (IC = 54.01 µg/ml) was the most potent urease inhibitor amongst the synthesized compounds and compared to standard thiourea (IC = 54.25 µg/ml). The most potent anticancer activity was shown by compounds T (IC = 3.84 μM) and T (IC = 3.25 μM) against HCT116 cell lines as compared to standard 5-FU (IC = 25.36 μM).
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http://dx.doi.org/10.1186/s13065-020-00717-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818921PMC
January 2021

Fibrinogen isoforms as potential blood-based biomarkers of Alzheimer's disease using a proteomics approach.

Int J Neurosci 2020 Dec 15:1-12. Epub 2020 Dec 15.

Collaborative Drug Discovery Research (CDDR) and Brain Degeneration and Therapeutics Research Group, Faculty of Pharmacy, University Teknologi MARA (UiTM) Cawangan Selangor, Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.

Alzheimer's disease (AD), the commonest form of dementia which is characterized by progressive decline in cognitive function, can only be definitively diagnosed after death. Although biomarkers may aid diagnosis, currently available AD biomarkers, which are predominantly based on cerebrospinal fluid and neuroimaging facilities, are either invasive or costly. Blood-based biomarkers for AD diagnosis are highly sought after due to its practicality at the clinic. This study was undertaken to determine the differential protein expression in plasma amongst Malaysian AD, mild cognitive impairment (MCI) and non-AD individuals. A proteomic approach which utilized two-dimensional differential in gel electrophoresis (2 D DIGE) was performed for blood samples from 15 AD, 14 MCI and 15 non-AD individuals. Mass spectrometry (MS)-based protein identification via MALDI ToF/ToF showed that fibrinogen-β-chain (spot 64) and fibrinogen-γ-chain (spot 91) with differential expression ratio >1.5 were significantly upregulated ( < 0.05) in AD patients when compared to non-AD individuals. Further data analysis using Pearson correlation found that the upregulated fibrinogen-γ-chain was weakly but significantly ( < 0.05) and inversely correlated with cognitive decline. Fibrinogen isoforms may play important roles in the vascular pathology of AD as well as neuroinflammation. As such, fibrinogen appears to be a promising blood-based biomarker for AD. Further validation of the present findings in larger population is now warranted.
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http://dx.doi.org/10.1080/00207454.2020.1860038DOI Listing
December 2020

High-performance thin layer chromatography-based phytochemical and bioactivity characterisation of anticancer endophytic fungal extracts derived from marine plants.

J Pharm Biomed Anal 2021 Jan 18;193:113702. Epub 2020 Oct 18.

Collaborative Drug Discovery Research (CDDR) Group, Faculty of Pharmacy, University Teknologi MARA (UiTM) Cawangan Selangor, Kampus Puncak Alam, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia. Electronic address:

Bioactive compounds from endophytic fungi exhibit diverse biological activities which include anticancer effect. Capitalising on the abundance of unexplored endophytes that reside within marine plants, this study assessed the anticancer potential of ethyl acetate endophytic fungal extracts (i.e. MBFT Tip 2.1, MBL 1.2, MBS 3.2, MKS 3 and MKS 3.1) derived from leaves, stem and fruits of marine plants that grow along Morib Beach, Malaysia. For identification of endophytic fungi, EF 4/ EF 3 and ITS 1/ ITS 4 PCR primer pairs were used to amplify the fungal 18S rDNA sequence and ITS region sequence, respectively. The resultant sequences were subjected to similarity search via the NCBI GenBank database. High-performance thin layer chromatography (HPTLC) hyphenated with bioassays was used to characterise the extracts in terms of their phytochemical profiles and bioactivity. Microchemical derivatisation was used to assess polyphenolic and phytosterol/ terpenoid content whereas biochemical derivatisation was used to establish antioxidant activities and α-amylase enzyme inhibition. The sulforhodamine B (SRB) assay was used to assess the anticancer effect of the extracts against HCT116 (a human colorectal cancer cell line). The present results indicated MBS 3.2 (Penicillium decumbens) as the most potent extract against HCT116 (IC = 0.16 μg/mL), approximately 3-times more potent than 5-flurouracil (IC = 0.46 μg/mL). Stepwise multiple regression method suggests that the anticancer effect of MBS 3.2 could be associated with high polyphenolic content and antioxidant potential. Nonlinear regression analysis confirmed that low to moderate α-amylase inhibition exhibits maximum anticancer activity. Current findings warrant further in-depth mechanistic studies.
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http://dx.doi.org/10.1016/j.jpba.2020.113702DOI Listing
January 2021

Adult Endogenous Dopaminergic Neuroregeneration Against Parkinson's Disease: Ideal Animal Models?

Neurotox Res 2021 Apr 3;39(2):504-532. Epub 2020 Nov 3.

Collaborative Drug Discovery Research (CDDR) Group and Brain Degeneration and Therapeutics Group, Faculty of Pharmacy, Universiti Teknologi MARA (UiTM) Cawangan Selangor, Kampus Puncak Alam, 42300, Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.

Parkinson's disease (PD) is the second most common neurodegenerative disease. The etiology of PD remains an enigma with no available disease modifying treatment or cure. Pharmacological compensation is the only quality of life improving treatments available. Endogenous dopaminergic neuroregeneration has recently been considered a plausible therapeutic strategy for PD. However, researchers have to first decipher the complexity of adult endogenous neuroregeneration. This raises the need of animal models to understand the underlying molecular basis. Mammalian models with highly conserved genetic homology might aid researchers to identify specific molecular mechanisms. However, the scarcity of adult neuroregeneration potential in mammals obfuscates such investigations. Nowadays, non-mammalian models are gaining popularity due to their explicit ability to neuroregenerate naturally without the need of external enhancements, yet these non-mammals have a much diverse gene homology that critical molecular signals might not be conserved across species. The present review highlights the advantages and disadvantages of both mammalian and non-mammalian animal models that can be essentially used to study the potential of endogenous DpN regeneration against PD.
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http://dx.doi.org/10.1007/s12640-020-00298-7DOI Listing
April 2021

Knowledge and Perception of Facial Candling for Allergic Rhinitis among University Staff and Students.

Evid Based Complement Alternat Med 2020 3;2020:5713134. Epub 2020 Aug 3.

Faculty of Pharmacy, Universiti Sultan Zainal Abidin, Besut, Terengganu, Malaysia.

Introduction: Facial candling is a traditional method used for relieving symptoms of allergic rhinitis (AR). This study aims to investigate the knowledge and perception of facial candling in a sample of staff and students in a public university in Malaysia.

Methods: An online questionnaire survey method was used. Based on sample size calculation, a total of 1,508 UiTM staff and students from ten selected campuses of Universiti Teknologi MARA (UiTM) were invited to participate in this survey. An up-to-date e-mail list of staff in the selected campuses was used as the sampling frame for the study, whereas the students were recruited from the official university student Facebook portal.

Results: A total of 788 respondents participated in this survey, 72.2% of them knew about facial candling, though only 35.4% had tried the treatment. Approximately one-fifth of respondents agreed that facial candling might treat AR. It was found that a higher number of users than nonusers agreed that facial candling was a traditional medicine (78.9% vs 55.0%); could be used on the face and ears (83.5% vs 45.4%); and could be self-administered at home (83.5 vs 45.4%). Interestingly, more than half of them were uncertain about its long-term effects and adverse reactions.

Conclusion: This study confirms the facial candling use among patients with AR although the percentage is low. The patients and general public need to be better informed about the use of facial candling in AR and its associated risks.
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http://dx.doi.org/10.1155/2020/5713134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422475PMC
August 2020

Synthesis, Characterization, Antimicrobial and Anticancer Studies of Metal Complexes of 2-methoxy-4-((3-methylpyridin-2-ylimino)methyl)phenol.

Mini Rev Med Chem 2020 ;20(13):1311-1317

Faculty of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, Haryana 124001, India.

Background: Being derived from primary amine and aromatic aldehyde, Schiff base and their complexes have an imperative role in the improvement of inorganic chemistry, which are broadly studied as coordination compounds and are gradually becoming more important in biochemical and analytical applications.

Methods: They have also been used for antibacterial, antifungal, anticancer, antitubercular activities. Novel synthesised Schiff's base 2-methoxy-4-((3-methylpyridin-2-ylimino)methyl)phenol (SB) and its metal complexes (Zn[II], Cu[II], Co[II] and Ni[II]) were characterised by UV, IR and NMR spectroscopy. Formation of the Schiff base and the metal (Zn[II], Cu[II], Co[II] and Ni[II]) chelates was supported by spectral and analytical data. The ligand and metal complexes have been screened for their antibacterial activity against Staphylococcus aureus, Salmonella typhi, Escherichia coli, Klebsiella pneumoniae and antifungal activity against the fungi Candida albicans and Aspergillus niger. Further, the synthesised compounds were also screened for antiproliferative activity against the human colorectal carcinoma (HCT116) cell line using the Sulforhodamine B assay.

Result: Metal complexes formed were found to enhance the potency of the Schiff base due to coordination with a copper complex, showing better activity than others.

Conclusion: Copper complex was observed to be more potent than other complexes against all the pathogenic microbes and cancer cell line (HCT116).
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http://dx.doi.org/10.2174/1389557520666200505124125DOI Listing
April 2021

Proteomics as a reliable approach for discovery of blood-based Alzheimer's disease biomarkers: A systematic review and meta-analysis.

Ageing Res Rev 2020 07 12;60:101066. Epub 2020 Apr 12.

Faculty of Pharmacy, University Teknologi MARA (UiTM) Cawangan Selangor, Kampus Puncak Alam, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia; Collaborative Drug Discovery Research (CDDR) Group, Pharmaceutical and Life Sciences Community of Research, Universiti Teknologi MARA (UiTM) Shah Alam, 40450 Shah Alam, Selangor Darul Ehsan, Malaysia. Electronic address:

In order to gauge the impact of proteomics in discovery of Alzheimer's disease (AD) blood-based biomarkers, this study had systematically reviewed articles published between 1984-2019. Articles that fulfilled the inclusion criteria were assessed for risk of bias. A meta-analysis was performed for replicable candidate biomarkers (CB). Of the 1651 articles that were identified, 17 case-control and two cohort studies, as well as three combined case-control and longitudinal designs were shortlisted. A total of 207 AD and mild cognitive impairment (MCI) CB were discovered, with 48 reported in >2 studies. This review highlights six CB, namely alpha-2-macroglobulin (α2M), pancreatic polypeptide (PP), apolipoprotein A-1 (ApoA-1), afamin, insulin growth factor binding protein-2 (IGFBP-2) and fibrinogen-γ-chain, all of which exhibited consistent pattern of regulation in >three independent cohorts. They are involved in AD pathogenesis via amyloid-beta (Aβ), neurofibrillary tangles, diabetes and cardiovascular diseases (CVD). Meta-analysis indicated that ApoA-1 was significantly downregulated in AD (SMD = -1.52, 95% CI: -1.89, -1.16, p < 0.00001), with low inter-study heterogeneity (I = 0%, p = 0.59). α2M was significantly upregulated in AD (SMD = 0.83, 95% CI: 0.05, 1.62, p = 0.04), with moderate inter-study heterogeneity (I = 41%, p = 0.19). Both CB are involved in Aβ formation. These findings provide important insights into blood-based AD biomarkers discovery via proteomics.
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http://dx.doi.org/10.1016/j.arr.2020.101066DOI Listing
July 2020

Synthesis, characterization, quantum chemical calculations and anticancer activity of a Schiff base NNOO chelate ligand and Pd(II) complex.

PLoS One 2020 14;15(4):e0231147. Epub 2020 Apr 14.

Faculty of Applied Sciences, Universiti Teknologi MARA, Shah Alam, Selangor, Malaysia.

This paper reports the synthesis, characterization, anticancer screening and quantum chemical calculation of a tetradentate Schiff base 2,2'-((1E,1'E)-((2,2-dimethylpropane-1,3-diyl)bis- (azanylylidene))bis(methanylylidene))bis(4-fluorophenol) (L2F) and its Pd (II) complex (PdL2F). The compounds were characterized via UV-Visible, NMR, IR spectroscopy and single crystal x-ray diffraction. Density Functional Theory (DFT) and time-dependent DFT calculations in gas and solvent phases were carried out using B3LYP, B3P86, CAM-B3LYP and PBE0 hybrid functionals combined with LanL2DZ basis set. Complexation of L2F to form PdL2F was observed to cause a bathochromic shift of the maximum absorption bands of n-π* from 327 to 410 nm; an upfield shift for δ (HC = N) from 8.30 to 7.96 ppm and a decreased wavenumber for ν(C = N) from 1637 to 1616 cm-1. Overall, the UV-Vis, NMR and IR spectral data are relatively well reproduced through DFT and TD-DFT methods. L2F and PdL2F showed IC50 of 90.00 and 4.10 μg/mL, respectively, against human colorectal carcinoma (HCT116) cell lines, signifying increased anticancer activity upon complexation with Pd (II).
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231147PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156068PMC
July 2020

antioxidant, antimicrobial and antiproliferative studies of four different extracts of , and .

Saudi J Biol Sci 2020 Jan 18;27(1):417-432. Epub 2019 Nov 18.

Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Cawangan Selangor, Kampus Puncak Alam, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.

Background: Medicinal plants are important source of drugs with pharmacological activities. Therefore, there is always rising demands to discover more therapeutic agents from various species. , and are high valued medicinal plants of Malaysia contain rich source of phenolic and flavonoid compounds. The aims of the present study were to evaluate anti-oxidant, antimicrobial and anti-proliferative effects on A549, HeGP2 and MCF7 cell lines of four different extracts of .

Methodology: The leaves of all selected plants were extracted with methanol, chloroform, ethyl acetate and butanol separately with simple cold maceration. Antioxidant activity of all crude extracts were quantitatively measured against DPPH and Ferric Reducing Assay. Antimicrobial evaluation was done by Microdilution and MTT assay and antipoliferative activity of all extracts of selected plant were evaluated against A549, HePG2 and MCF7 cell lines.

Results: Results showed that methanol extract exhibited highest percentage free radical scavenging activity of almost all extracts of selected plants. Antimicrobials results showed chloroform and methanol extracts of extract were the two most active extracts against resistant MRSA but not . Only methanol extract of showed antimicrobial activity against the tested pathogens. Chloroform and methanol extracts of elicited antimicrobial activity against but not MRSA. Antiproliferative activity against three tested cell lines results showed that ethyl acetate extract of showed good effect whereas methanol extract of and exhibited good antiproliferative activity.

Conclusions: The results of the present investigation demonstrated significant variations in the antioxidant, antimicrobial and antiproliferative effects of different solvent extracts. These data could be helpful in isolation of pure potent compounds with good biological activities from the extracts of plants.
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http://dx.doi.org/10.1016/j.sjbs.2019.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933182PMC
January 2020

HPTLC based approach for bioassay-guided evaluation of antidiabetic and neuroprotective effects of eight essential oils of the Lamiaceae family plants.

J Pharm Biomed Anal 2020 Jan 4;178:112909. Epub 2019 Oct 4.

School of Pharmacy and Applied Science, La Trobe Institute for Molecular Sciences, La Trobe University, Edwards Rd, Bendigo, 3550, Australia; Department of Pharmaceutical and Toxicological Chemistry, I. M. Sechenov First Moscow State Medical University (Sechenov University), Bolshaya Pirogovskaya 2, p 4, 119991, Moscow, Russia. Electronic address:

A high-performance thin-layer chromatography (HPTLC) method combined with effect-directed-analysis (EDA) was developed to screen the antioxidant, neuroprotective and antidiabetic effects in essential oils derived from lavender flower, lemon myrtle, oregano, peppermint, sage, and rosemary leaves (Lamiaceae family). HPTLC hyphenated with microchemical (DPPH•, p-anisaldehyde, and ferric chloride) derivatizations, was used to evaluate antioxidant activity, presence of phytosterols and terpenoids, and polyphenolic content, while the combination with biochemical (α-amylase and acetylcholine esterase (AChE) enzymatic) derivatizations was used to asses α-amylase and AChE inhibitory activities. The superior antioxidant activity of oregano leaf extract is attributed to the presence of high levels of aromatic compounds, like polyphenolic acids. The strongest α-amylase inhibition was observed in lemon myrtle and rosemary plus extracts due to the presence of monoterpenes. Rosemary and sage extracts exhibit the highest AChE inhibition activity, with 1 μL essential oils being more potent than the recommended daily dose of donepezil. This superior neuroprotection was attributed to the presences of di- and triterpenes that displayed strong AChE inhibition and antioxidant potential in DPPH• free radical assay. Antioxidant activity was related to phenolic content (R = 0.49), while α-amylase inhibitory activity was positively related to antioxidant activity (R = 0.20) and terpenoid/sterol content (R = 0.31). AChE inhibitory activity was correlated (R = 0.80) to the combined effect of phenolics and terpenoids. Thus, the superior AChE inhibitory and neuroprotection potential of rosemary and sage essential oils could be attributed to joint effects of main phenolic and terpene constituents. The hyphenated HPTLC method provided rapid bioanalytical profiling of highly complex essential oil samples.
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http://dx.doi.org/10.1016/j.jpba.2019.112909DOI Listing
January 2020

Synthesis, molecular docking and biological potentials of new 2-(4-(2-chloroacetyl) piperazin-1-yl)--(2-(4-chlorophenyl)-4-oxoquinazolin-3(4)-yl)acetamide derivatives.

BMC Chem 2019 Dec 5;13(1):113. Epub 2019 Sep 5.

5Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraidah, 51452 Kingdom of Saudi Arabia.

In the present study, a series of 2-(4-(2-chloroacetyl)piperazin-1-yl)--(2-(4-chlorophenyl)-4-oxoquinazolin-3(4)-yl)acetamide derivatives was synthesized and its chemical structures were confirmed by physicochemical and spectral characteristics. The synthesized compounds were evaluated for their in vitro antimicrobial (tube dilution technique) and anticancer (MTT assay) activities along with molecular docking study by Schrodinger 2018-1, maestro . The antimicrobial results indicated that compounds , , and displayed the significant antimicrobial activity and comparable to the standards drugs (ciprofloxacin and fluconazole). The anticancer activity results indicated that compound have good anticancer activity among the synthesized compounds but lower active than the standard drugs (5-fluorouracil and tomudex). Molecular docking study demonstrated that compounds and displayed the good docking score with better anticancer potency within the binding pocket and these compounds may be used as a lead for rational drug designing for the anticancer molecules.
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http://dx.doi.org/10.1186/s13065-019-0629-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727350PMC
December 2019

In-silico molecular design of heterocyclic benzimidazole scaffolds as prospective anticancer agents.

BMC Chem 2019 Dec 11;13(1):90. Epub 2019 Jul 11.

1Faculty of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, 124001 India.

Benzimidazole is a valuable pharmacophore in the field of medicinal chemistry and exhibit wide spectrum of biological activity. Molecular docking technique is routinely used in modern drug discovery for understanding the drug-receptor interaction. The selected data set of synthesized benzimidazole compounds was evaluated for its in vitro anticancer activity against cancer cell lines (HCT116 and MCF7) by sulforhodamine B (SRB) assay. Further, molecular docking study of data set was carried out by Schrodinger-Maestro 5 using CDK-8 (PDB code: 5FGK) and ER-alpha (PDB code: 3ERT) as possible target for anticancer activity. Molecular docking results demonstrated that compounds , , , and displayed good docking score with better interaction within crucial amino acids and corelate to their anticancer results. ADME results indicated that compounds , and have significant results within the close agreement of the Lipinski's rule of five and Qikprop rule within the range and these compounds may be taken as lead molecules for the discovery of new anticancer agents.
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http://dx.doi.org/10.1186/s13065-019-0608-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661772PMC
December 2019

Molecular docking, synthesis and biological significance of pyrimidine analogues as prospective antimicrobial and antiproliferative agents.

BMC Chem 2019 Dec 9;13(1):85. Epub 2019 Jul 9.

5Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraidah, 51452 Kingdom of Saudi Arabia.

Pyrimidine nucleus is a significant pharmacophore that exhibited excellent pharmacological activities. A series of pyrimidine scaffolds was synthesized and its chemical structures were confirmed by physicochemical and spectral analysis. The synthesized compounds were evaluated for their antimicrobial potential towards Gram positive and negative bacteria as well as fungal species. They were also assessed for their anticancer activity toward a human colorectal carcinoma cell line (HCT116). Whilst results of antimicrobial potential revealed that compounds , , and exhibited better activity against tested microorganisms, the results of antiproliferative activity indicated that compounds and showed excellent activity against HCT116. Further, the molecular docking of pyrimidine derivatives , and with CDK8 (PDB id: 5FGK) protein indicated that moderate to better docking results within the binding pocket. Compounds and having significant antimicrobial and anticancer activities may be selected as lead compounds for the development of novel antimicrobial and anticancer agent, respectively.
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http://dx.doi.org/10.1186/s13065-019-0601-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661814PMC
December 2019

4-(4-Bromophenyl)-thiazol-2-amine derivatives: synthesis, biological activity and molecular docking study with ADME profile.

BMC Chem 2019 Dec 23;13(1):60. Epub 2019 Apr 23.

5Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraidah, 51452 Kingdom of Saudi Arabia.

In order to overcome the challenges of microbial resistance as well as to improve the effectiveness and selectivity of chemotherapeutic agents against cancer, a novel series of 4-(4-bromophenyl)-thiazol-2-amine derivatives was synthesized and its molecular structures were confirmed by physicochemical and spectral characteristics. The synthesized compounds were further evaluated for their in vitro antimicrobial activity using turbidimetric method and anticancer activity against oestrogen receptor positive human breast adenocarcinoma cancer cell line (MCF7) by Sulforhodamine B (SRB) assay. The antimicrobial activity results revealed that compound , , and exhibited promising antimicrobial activity that are comparable to standard norfloxacin (antibacterial) and fluconazole (antifungal). Anticancer screening results demonstrated that compound was found to be the most active one against cancer cell line when compared to the rest of the compounds and comparable to the standard drug (5-fluorouracil). The molecular docking study demonstrated that compounds, , , and displayed good docking score within binding pocket of the selected PDB ID (1JIJ, 4WMZ and 3ERT) and showed promising ADME properties.
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http://dx.doi.org/10.1186/s13065-019-0575-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661755PMC
December 2019

Design, synthesis and biological profile of heterocyclic benzimidazole analogues as prospective antimicrobial and antiproliferative agents.

BMC Chem 2019 Dec 3;13(1):50. Epub 2019 Apr 3.

1Faculty of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, 124001 India.

Background: Nitrogen containing heterocycles are widely used and investigated by pharmaceutical industry, as they are important in discovery and designing of new drug molecules. Drugs with a benzimidazole nucleus possess exclusive structural features and electron-rich atmosphere, which enable them to bind to a number of biologically important targets and result in a wide range of activities. This has served as the basis of the present study whereby new scaffolds with benzimidazole moiety were designed and synthesized.

Methods: The structures of synthesized compounds were confirmed by physicochemical and spectral means. The synthesized compounds were screened for their antimicrobial and antiproliferative activities by tube dilution and Sulforhodamine B (SRB) assays, respectively.

Results And Conclusion: The in vitro biological screening results revealed that compound exhibited promising antimicrobial and anticancer activities which are comparable to standards.
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http://dx.doi.org/10.1186/s13065-019-0567-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661758PMC
December 2019

Synthesis, molecular modelling and biological significance of -(4-(4-bromophenyl) thiazol-2-yl)-2-chloroacetamide derivatives as prospective antimicrobial and antiproliferative agents.

BMC Chem 2019 Dec 1;13(1):46. Epub 2019 Apr 1.

5Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraidah, 51452 Kingdom of Saudi Arabia.

To combat the antimicrobial and anticancer drug resistance by pathogens and cancerous cells, efforts has been made to study the pharmacological activities of newly synthesized -(4-(4-bromophenyl)thiazol-2-yl)-2-chloroacetamide derivatives. The molecular structures of the synthesized derivatives were confirmed by their physicochemical properties and spectroanalytical data (NMR, IR and elemental). The synthesized compounds were evaluated for their in vitro antimicrobial activity against bacterial (Gram positive and Gram negative) and fungal species using turbidimetric method and anticancer activity against oestrogen receptor positive human breast adenocarcinoma cancer cell line (MCF7) by Sulforhodamine B (SRB) assay. Molecular docking studies were carried out to study the binding mode of active compounds with receptor using Schrodinger The antimicrobial activity results revealed that compounds , and have promising antimicrobial activity. Anticancer screening results indicated that compounds and were found to be the most active ones against breast cancer cell line. Furthermore, the molecular docking study demonstrated that compounds , , , and displayed good docking score within binding pocket of the selected PDB ID (1JIJ, 4WMZ and 3ERT) and has the potential to be used as lead compounds for rational drug designing.
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http://dx.doi.org/10.1186/s13065-019-0564-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661967PMC
December 2019

4-(2-(1-Benzo[]imidazol-2-ylthio)acetamido)--(substituted phenyl)benzamides: design, synthesis and biological evaluation.

BMC Chem 2019 Dec 2;13(1):12. Epub 2019 Feb 2.

1Faculty of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, 124001 India.

Background: Dihydrofolate reductase (DHFR) is an important target for antimetabolite class of antimicrobials because it participates in purine synthesis. 2-mercaptobenzimidazole (2MBI) has similar structural features as purine nucleotides. Given that benzimidazole and similar heteroaromatics have been broadly examined for their anticancer potential, so, we hereby report the design, synthesis and biological studies (i.e. antimicrobial and anticancer studies) of 2MBI derivatives.

Methodology: The antimicrobial activity of synthesized 2MBI derivatives were evaluated against Gram positive and Gram negative bacterial species as well as fungal species by tube dilution technique whereas their anticancer activity was assessed against human colorectal carcinoma cell line (HCT116) by Sulforhodamine B (SRB) assay. They were also structurally characterized by IR, NMR, MS and elemental analyses.

Results Discussion And Conclusion: The antimicrobial activity findings revealed that compound (MIC  = 1.27, 2.54, 1.27 µM), (MIC = 1.43 µM), (MIC = 2.60 µM), and (MIC = 2.65 µM) exhibited significant antimicrobial effects against tested strains, i.e. Gram-positive, Gram-negative (bacterial) and fungal strains. The anticancer screening results demonstrated that compounds , (IC = 5.85, 4.53 µM) were the most potent compounds against cancer cell line (HCT116) even more than 5-FU, the standard drug (IC = 9.99 µM).
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http://dx.doi.org/10.1186/s13065-019-0533-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661798PMC
December 2019

Computational approaches: discovery of GTPase HRas as prospective drug target for 1,3-diazine scaffolds.

BMC Chem 2019 Dec 24;13(1):96. Epub 2019 Jul 24.

5Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraidah, 51452 Kingdom of Saudi Arabia.

Heterocyclic 1,3-diazine nucleus is a valuable pharmacophore in the field of medicinal chemistry and exhibit a wide spectrum of biological activities. PharmMapper, a robust online tool used for establishing the target proteins based on reverse pharmacophore mapping. PharmMapper study is carried out to explore the pharmacological activity of 1,3-diazine derivatives using reverse docking program. PharmMapper, an open web server was used to recognize for all the feasible target proteins for the developed compounds through reverse pharmacophore mapping. The results were analyzed via molecular docking with maestro (Schrodinger 2018-1) using GTPase HRas as possible target. The molecular docking studies displayed the binding behavior of 1,3-diazine within GTP binding pocket. From the docking study compounds and showed better docked score with anticancer potency against cancer cell line (HCT116). Hence, the GTPase HRas may be the possible target of 1,3-diazine derivatives for their anticancer activity where the retrieved information may be quite useful for developing rational drug designing. Furthermore the selected 1,3-diazine compounds were evaluated for their in vitro anticancer activity against murine macrophages cell line. 1,3-Diazine compounds exhibited good selectivity of the compounds towards the human colorectal carcinoma cell line instead of the murine macrophages. The toxicity study of the most active compounds was also performed on non cancerous HEK-293 cell line.
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http://dx.doi.org/10.1186/s13065-019-0613-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6659553PMC
December 2019

In vitro assessment of pediococci- and lactobacilli-induced cholesterol-lowering effect using digitally enhanced high-performance thin-layer chromatography and confocal microscopy.

Anal Bioanal Chem 2019 Feb 24;411(6):1181-1192. Epub 2019 Jan 24.

Faculty of Pharmacy, University Teknologi MARA (UiTM), 42300, Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.

The cholesterol-lowering properties of 12 lactic acid bacteria (LAB) in the absence or presence of 0.3% bile salts were assessed and compared quantitatively and qualitatively in vitro. A new, more sensitive and cost-effective high-performance thin-layer chromatography method combined with digital image evaluation of derivatised chromatographic plates was developed and validated to quantify cholesterol in LAB culture media. The performance of the method was compared with that of the o-phthalaldehyde method. For qualitative assessment, assimilated fluorescently tagged cholesterol was visualised by confocal microscopy. All LAB strains exhibited a cholesterol-lowering effect of various degrees (19-59% in the absence and 14-69% in the presence of bile salts). Lactobacillus plantarum LAB12 and Pentosaceus pentosaceus LAB6 were the two best strains of lactobacilli and pediococci. They lowered cholesterol levels by 59% and 54%, respectively, in the absence and by 69% and 58%, respectively, in the presence of bile salts. Confocal microscopy showed that cholesterol was localised at the outermost cell membranes of LAB12 and LAB6. The present findings warrant in-depth in vivo study. Graphical abstract (A) 3D plots based on scan at 525 nm of (B) derivatized HPTLC plate of separated cholesterol and (C) confocal microscopic image showing the localisation of NBD-cholesterol assimilated by LAB.
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http://dx.doi.org/10.1007/s00216-018-1544-2DOI Listing
February 2019

Design, synthesis and therapeutic potential of 3-(2-(1H-benzo[d]imidazol-2-ylthio)acetamido)-N-(substituted phenyl)benzamide analogues.

Chem Cent J 2018 Dec 19;12(1):139. Epub 2018 Dec 19.

Faculty of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, 124001, India.

Background: The emergence of bacterial resistance is a major public health problem. It is essential to develop and synthesize new therapeutic agents with better activity. The mode of actions of certain newly developed antimicrobial agents, however, exhibited very limited effect in treating life threatening systemic infections. Therefore, the advancement of multi-potent and efficient antimicrobial agents is crucial to overcome the increased multi-drug resistance of bacteria and fungi. Cancer, which remains as one of the primary causes of deaths and is commonly treated by chemotherapeutic agents, is also in need of novel and efficacious agents to treat resistant cases. As such, a sequence of novel substituted benzamides was designed, synthesized and evaluated for their antimicrobial and anticancer activities.

Methodology: All synthesized compounds were characterized by IR, NMR, Mass and elemental analysis followed by in vitro antimicrobial studies against Gram-positive (Staphylococcus aureus), Gram-negative (Salmonella typhi and Klebsiella pneumoniae) bacterial and fungal (Candida albicans and Aspergillus niger) strains by the tube dilution method. The in vitro anticancer evaluation was carried out against the human colorectal carcinoma cell line (HCT116), using the Sulforhodamine B assay.

Results, Discussion And Conclusion: Compound W6 (MIC = 5.19 µM) emerged as a significant antibacterial agent against all tested bacterial strains i.e. Gram-positive (S. aureus), Gram-negative (S. typhi, K. pneumoniae) while compound W1 (MIC = 5.08 µM) was most potent against fungal strains (A. niger and C. albicans) and comparable to fluconazole (MIC = 8.16 µM). The anticancer screening demonstrated that compound W17 (IC = 4.12 µM) was most potent amongst the synthesized  compounds and also more potent than the standard drug 5-FU (IC = 7.69 µM).
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http://dx.doi.org/10.1186/s13065-018-0513-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767998PMC
December 2018

Facial Candling for the Treatment of Allergic Rhinitis in Young Adults: A Qualitative Study.

J Pharm Bioallied Sci 2018 Oct-Dec;10(4):199-207

School of Pharmacy, Management & Science University, Shah Alam, Malaysia.

Aims: Facial candling is one of the traditional treatments that is claimed to be able to help in curing or reducing various allergy and inflammation conditions such as allergic rhinitis. We aimed to explore the perceptions of participants with allergic rhinitis toward their disease conditions and facial candling treatment.

Materials And Methods: The study used a qualitative exploratory design, comprising 12 in-depth interviews. A semi-structured topic guide was used to explore all relevant aspects of the topic, which were audio recorded, transcribed verbatim. All the interviews were conducted in a few beauty salons in purposively selected city areas in the state of Kedah, Malaysia.

Results: Of the 12 patients, seven (58%) reported a positive experience of facial candling treatment, with improvement in the condition of their allergic rhinitis. Specific themes about the experience of facial candling treatment that were identified within the transcript data included knowledge about facial candling, options for disease treatment, effectiveness of facial candling, sources of information, comparison, application of treatment, treatment budget, and safety. The major strength lies in the fact that reasons for using facial candling were uncovered from the perspectives of people with allergic rhinitis through the in-depth interviews.

Conclusions: The motives of these participants for using facial candling are mainly due to cultural influence and its low cost of treatment. There were mixed responses from the participants about the usefulness of facial candling. Most of the respondents had not assessed the safety of prolonged use of facial candling and regarded it as a safe procedure as this has been practiced for generations.
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http://dx.doi.org/10.4103/JPBS.JPBS_33_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266643PMC
December 2018

Design, Synthesis and Therapeutic Potential of Some 6, 6'-(1,4- phenylene)bis(4-(4-bromophenyl)pyrimidin-2-amine)analogues.

Mini Rev Med Chem 2019 ;19(7):609-621

Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.

Background: A series of 6, 6'-(1,4-phenylene)bis(4-(4-bromophenyl)pyrimidin-2-amine) derivatives has been synthesized by Claisen-Schmidt condensation and its chemical structures was confirmed by FT-IR, 1H/13C-NMR spectral and elemental analyses. The molecular docking study was carried out to find the interaction between active bis-pyrimidine compounds with CDK-8 protein. The in vitro antimicrobial potential of the synthesized compounds was determined against Gram-positive and Gram-negative bacterial species as well fungal species by tube dilution technique. Antimicrobial results indicated that compound 11y was found to be most potent one against E. coli (MICec = 0.67 µmol/mL) and C. albicans (MICca = 0.17 µmol/mL) and its activity was comparable to norfloxacin (MIC = 0.47 µmol/mL) and fluconazole (MIC = 0.50 µmol/mL), respectively.

Conclusion: Anticancer screening of the synthesized compounds using Sulforhodamine B (SRB) assay demonstrated that compounds 2y (IC50 = 0.01 µmol/mL) and 4y (IC50= 0.02 µmol/mL) have high antiproliferative potential against human colorectal carcinoma cancer cell line than the reference drug (5- fluorouracil) and these compounds also showed best dock score with better potency within the ATP binding pocket and may also be used lead for rational drug designing.
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http://dx.doi.org/10.2174/1389557519666181210162413DOI Listing
April 2019

Synthesis and biological profile of substituted benzimidazoles.

Chem Cent J 2018 Dec 1;12(1):125. Epub 2018 Dec 1.

Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraidah, 51452, Kingdom of Saudi Arabia.

Background: A series of benzimidazole derivatives was developed and its chemical scaffolds were authenticated by NMR, IR, elemental analyses and physicochemical properties. The synthesized compounds were screened for their antimicrobial and antiproliferative activities.

Results And Discussion: The synthesized benzimidazole compounds were evaluated for their antimicrobial activity using the tube dilution method and were found to exhibit good antimicrobial potential against selected Gram negative and positive bacterial and fungal species. The compounds were also assessed for their anticancer activity exhibited using the SRB assay and were found to elicit antiproliferative activity against MCF7 breast cancer cell line, which was comparable to the standard drug.

Conclusion: Antimicrobial screening results indicated that compounds 1, 2 and 19 to be promising antimicrobial agents against selected microbial species and comparable to standard drugs which included norfloxacin and fluconazole. The anticancer screening results revealed that compounds, 12, 21, 22 and 29 to show the highest activity against MCF7 and their IC values were more potent than 5-fluorouracil.
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http://dx.doi.org/10.1186/s13065-018-0498-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768139PMC
December 2018

Design, synthesis and biological evaluation of 3-(2-aminooxazol-5-yl)-2H-chromen-2-one derivatives.

Chem Cent J 2018 Dec 4;12(1):130. Epub 2018 Dec 4.

Faculty of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, 124001, India.

Background: In view of wide range of biological activities of oxazole, a new series of oxazole analogues was synthesized and its chemical structures were confirmed by spectral data (Proton/Carbon-NMR, IR, MS etc.). The synthesized oxazole derivatives were screened for their antimicrobial and antiproliferative activities.

Results And Discussion: The antimicrobial activity was performed against selected fungal and bacterial strains using tube dilution method. The antiproliferative potential was evaluated against human colorectal carcinoma (HCT116) and oestrogen- positive human breast carcinoma (MCF7) cancer cell lines using Sulforhodamine B assay and, results were compared to standard drugs, 5-fluorouracil and tamoxifen, respectively.

Conclusion: The performed antimicrobial activity indicated that compounds 3, 5, 6, 8 and 14 showed promising activity against selected microbial species. Antiproliferative screening found compound 14 to be the most potent compound against HCT116 (IC = 71.8 µM), whereas Compound 6 was the most potent against MCF7 (IC = 74.1 µM). Further, the molecular docking study has been carried to find out the interaction between active oxazole compounds with CDK8 (HCT116) and ER-α (MCF7) proteins indicated that compound 14 and 6 showed good dock score with better potency within the ATP binding pocket and may be used as a lead for rational drug designing of the anticancer molecule.
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http://dx.doi.org/10.1186/s13065-018-0499-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768039PMC
December 2018

Synthesis, biological evaluation and corrosion inhibition studies of transition metal complexes of Schiff base.

Chem Cent J 2018 Nov 20;12(1):117. Epub 2018 Nov 20.

Faculty of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, 124001, India.

Background: The transition metal complexes formed from Schiff base is regarded as leading molecules in medicinal chemistry. Because of the preparative availability and diversity in the structure of central group, the transition metals are important in coordination chemistry. In the present work, we have designed and prepared Schiff base and its metal complexes (MC-MC) and screened them for antimicrobial, anticancer and corrosion inhibitory properties.

Methodology: The synthesized metal complexes were characterized by physicochemical and spectral investigation (UV, IR, H and C-NMR) and were further evaluated for their antimicrobial (tube dilution) and anticancer (SRB assay) activities. In addition, the corrosion inhibition potential was determined by electrochemical impedance spectroscopy (EIS) technique.

Results And Discussion: Antimicrobial screening results found complexes (MC-MC) to exhibit less antibacterial activity against the tested bacterial species compared to ofloxacin while the complex MC exhibited greater antifungal activity than the fluconazole. The anticancer activity results found the synthesized Schiff base and its metal complexes to elicit poor cytotoxic activity than the standard drug (5-fluorouracil) against HCT116 cancer cell line. Metal complex MC showed more corrosion inhibition efficiency with high R values and low C values.

Conclusion: From the results, we can conclude that complexes MC and MC may be used as potent antimicrobial and anticorrosion agents, respectively.
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http://dx.doi.org/10.1186/s13065-018-0487-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768142PMC
November 2018

Reverse pharmacophore mapping and molecular docking studies for discovery of GTPase HRas as promising drug target for bis-pyrimidine derivatives.

Chem Cent J 2018 Oct 22;12(1):106. Epub 2018 Oct 22.

Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraidah, 51452, Saudi Arabia.

Background: Pyrimidine is an important pharmacophore in the field of medicinal chemistry and exhibit a broad spectrum of biological potentials. A study was carried out to identify the target protein of potent bis-pyrimidine derivatives using reverse docking program. PharmMapper, a robust online tool was used for identifying the target proteins based on reverse pharmacophore mapping. The murine macrophage (RAW 264.7) and human embryonic kidney (HEK-293) cancer cell line used for selectivity and safety study.

Methods: An open web server PharmMapper was used to identify the possible target of the developed compounds through reverse pharmacophore mapping. The results were analyzed and validated through docking with Schrodinger v9.6 using 10 protein GTPase HRas selected as possible target. The docking studies with Schrödinger validated the binding behavior of bis-pyrimidine compounds within GTP binding pocket. MTT and sulforhodamine assay were used as antiproliferative activity.

Results And Discussion: The protein was found one of the top scored targets of the compound 18, hence, the GTPase HRas protein was found crucial to be targeted for competing cancer. Toxicity study demonstrated the significant selectivity of most active compounds, 12, 16 and 18 showed negligible cell toxicity at their IC concentration.

Conclusion: From the results, we may conclude that GTPase HRas as a possible target of studied bis-pyrimidine derivatives where the retrieved information may be quite useful for rational drug designing.
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http://dx.doi.org/10.1186/s13065-018-0475-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768019PMC
October 2018

2-Mercaptobenzimidazole Schiff Bases: Design, Synthesis, Antimicrobial Studies and Anticancer Activity on HCT-116 Cell Line.

Mini Rev Med Chem 2019 ;19(13):1080-1092

Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.

Background: Increased rate of mortality due to the development of resistance to currently available antimicrobial and anticancer agents initiated the need to develop new chemical entities for the treatment of microbial infections and cancer.

Objective: The present study was aimed to synthesize and evaluate antimicrobial and anticancer activities of Schiff bases of 2-mercaptobenzimidazole.

Methods: The Schiff bases of 2-mercaptobenzimidazole were synthesized from 4-(2-(1H-benzo[d]- imidazol-2-ylthio)acetamido)benzohydrazide. The synthesized compounds were evaluated for antimicrobial and anticancer activities by tube dilution method and Sulforhodamine-B (SRB) assay, respectively.

Results: Compounds 8 (MICpa, an = 2.41, 1.20 µM/ml), 10 (MICse, sa = 2.50 µM/ml), 20 (MICec = 2.34 µM/ml) and 25 (MICca = 1.46 µM/ml) showed significant antimicrobial activity against tested bacterial and fungal strains and compounds 20 (IC50 = 8 µg/ml) and 23 (IC50 = 7 µg/ml) exhibited significant anticancer activity.

Conclusion: In general, the synthesized derivatives exhibited moderate antimicrobial and anticancer activities. Compounds 8 and 25 having high antifungal potential among the synthesized compounds may be taken as lead molecules for the development of novel antifungal agents.
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http://dx.doi.org/10.2174/1389557518666181009151008DOI Listing
October 2019