Publications by authors named "Aamer Saeed"

211 Publications

Effect of organic solvents on solvatochromic, fluorescence, and electrochemical properties of synthesized thiazolylcoumarin derivatives.

Luminescence 2021 Mar 23. Epub 2021 Mar 23.

Department of Chemistry Division of Science and Technology University of Education Lahore, Pakistan.

In this present investigation, thiazolylcoumarin derivatives (5a-5k) were synthesized from thiosemicarbazide, ethyl acetoacetate, and naphthaldehyde through a multistep route. The formation of thiazolylcoumarin derivatives with bioactive scaffolds was confirmed through nuclear magnetic resonance spectroscopy. A solvatochromic study of synthesized thiazolylcoumarin derivatives was carried out using ultraviolet-visible methods for dimethylformamide (DMF), ethyl acetate, and ethanol solvents. The redox behaviour of as-synthesized thiazolylcoumarin derivatives (5a-5k) was examined in dimethyl sulphoxide by conducting an electrochemical study. Fluorescence properties of thiazolylcoumarin derivatives were studied in DMF, ethanol, and ethyl acetate to visualize the solvent effect on the emitting ability of thiazolylcoumarin derivatives.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/bio.4044DOI Listing
March 2021

Synthesis, X-ray, Hirshfeld surface analysis, exploration of DNA binding, urease enzyme inhibition and anticancer activities of novel adamantane-naphthyl thiourea conjugate.

Bioorg Chem 2021 Apr 9;109:104707. Epub 2021 Feb 9.

Hacettepe University, Department of Physics, 06800 Beytepe-Ankara, Turkey.

1-(adamantane-1-carbonyl-3-(1-naphthyl)) thiourea (CHNOS (4), was synthesized by the reaction of freshly prepared adamantane-1-carbonyl chloride from corresponding acid (3) with ammonium thiocyanate in 1:1 M ratio in dry acetone to afford the adamantane-1-carbonyl isothiocyanate (2) in situ followed by treatment with 1-naphthyl amine (3). The structure was established by elemental analyses, FTIR, H, C NMR and mass spectroscopy. The molecular and crystal structure were determined by single crystal X-ray analysis. It belongs to triclinic system P - 1 space group with a = 6.7832(5) Å, b = 11.1810(8) Å, c = 13.6660(10) Å, α = 105.941(6)°, β = 103.730(6)°, γ = 104.562(6)°, Z = 2, V = 910.82(11) Å. The naphthyl group is almost planar. In the crystal structure, intermolecular CH···O hydrogen bonds link the molecules into centrosymmetric dimers, enclosing R(14) ring motifs, while the intramolecular NH···O hydrogen bonds enclose S(6) ring motifs, in which they may be effective in the stabilization of the structure. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H … H (59.3%), H … C/C … H (19.8%) and H … S/S … H (10.1%) interactions. Hydrogen bonding and van der Waals interactions are the dominant interactions in the crystal packing. DFT, molecular docking and urease inhibition studies revealed stability and electron withdrawing nature of 4 as compared to DNA base pairs and residues of urease. The DNA binding results from docking, UV- visible spectroscopy, and viscosity studies indicated significant binding of 4 with the DNA via intercalation and groove binding. Further investigation of the compound was done on hepatocellular carcinoma; Huh-7 cell line as well as normal human embryonic kidney; Hek-293 cell line. The compound showed significant cytotoxic activity against Huh-7 cells in comparison to normal Hek-293 cells indicating selective cytotoxicity towards cancer cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2021.104707DOI Listing
April 2021

Editorial: Chemical Insights Into the Synthetic Chemistry of Quinazolines and Quinazolinones: Recent Advances.

Front Chem 2020 4;8:641321. Epub 2021 Feb 4.

Department of Chemistry, Quaid-i-Azam University, Islamabad, Pakistan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fchem.2020.641321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890182PMC
February 2021

Chemical Insights Into the Synthetic Chemistry of Quinazolines: Recent Advances.

Front Chem 2020 14;8:594717. Epub 2021 Jan 14.

Department of Chemistry, Quaid-i-Azam University, Islamabad, Pakistan.

In medicinal chemistry, one of the most significant heterocyclic compounds are quinazolines, possessing broad range of biological properties such as anti-bacterial, anti-fungal, anti-HIV, anti-cancer, anti-inflammatory, and analgesic potencies. Owing to its numerous potential applications, in the past two decades, there is an increase in the importance of designing novel quinazolines, exploring promising routes to synthesize quinazolines, investigating different properties of quinazolines, and seeking for potential applications of quinazolines. The present review article describes synthesis of quinazolines eco-friendly, mild, atom-efficient, multi-component synthetic strategies reported in the literature. The discussion is divided into different parts as per the key methods involved in the formation of quinazoline skeletons, aiming to provide readers an effective methodology to a better understanding. Consideration has been taken to cover the most recent references. Expectedly, the review will be advantageous in future research for synthesizing quinazolines and developing more promising synthetic approaches.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fchem.2020.594717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873916PMC
January 2021

Highly productive and scalable approach to synthesize ticlopidine: A potent thienopyridine anti-platelet aggregation drug.

Heliyon 2020 Dec 16;6(12):e05731. Epub 2020 Dec 16.

Department of Chemistry, Quaid-i-Azam University, Islamabad, Pakistan.

Ticlopidine (trade name Ticlid), an acidic thienopyridine derivative, is an effective, well-known and long-acting inhibitor of platelet aggregation. Because of its potent inhibitory activity for treating a variety of diseases, the development of efficient approaches for accessing ticlopidine represents an important endeavour. Therefore, in this research work, we developed a promising novel five-step synthetic approach for synthesizing ticlopidine. This method provides ticlopidine in 60% overall yield from readily available starting material thiophene. In this methodology, all steps afforded excellent yields and are operationally simple and environmentally acceptable. This approach also offers various attractive advantages, for example, it's applicable for large-scale synthesis, has simple work-up procedures and short reaction times, and uses inexpensive and readily available reagents. Furthermore, 4,5,6,7-tetrahydrothieno[3,2-c]pyridine is a key precursor for the synthesis of numerous bioactive compounds such as prasugrel and clopidogrel. This protocol provides 4,5,6,7-tetrahydrothieno[3,2-c]pyridine in 62% overall yield a 4-step synthetic approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.heliyon.2020.e05731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750374PMC
December 2020

Identification of novel C-2 symmetric Bis-Azo-Azamethine molecules as competitive inhibitors of mushroom tyrosinase and free radical scavengers: synthesis, kinetics, and molecular docking studies.

J Biomol Struct Dyn 2020 Dec 20:1-10. Epub 2020 Dec 20.

International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang, China.

Tyrosinase is a multi-copper enzyme found in plants, animals and microorganisms, plays a critical role in the melanogenesis and browning process critical to cosmetics and food industries. Many natural, semi-synthetic and synthetic inhibitors have been discovered. To this end, a small library of symmetrical Bis-Azo-Azamethine hybrids was synthesized and characterized through spectroscopic and analytical data and explored for mushroom tyrosinase and free radical scavenging activity. All of the molecules explicated better potential compared to the standard Kojic acid. On the whole, compound having IC value 0.002 ± 0.004 µM was found to be the most potent derivative. The Kinetic studies were performed for and indicating the mode of inhibition in a competitive manner. Structure Activity Relationship (SAR) analysis and docking studies were carried out. Thus compound bearing bulky naphthyl groups was most potent and, The molecular docking indicated formation of two hydrogen bonds with Arg268 and one hydrophobic interaction with Glu322. The carbonyl oxygen of interacts with Arg268 and form two hydrogen bonds having lengths 2.44 and 2.62 Å, respectively. In the same way, compounds were appraised for DPPH free radical scavenging ability and five of them , , , and were found to exhibit higher % scavenging potency compared with vitamin C, as the standard. Interesting compound was again the most potent in the series. The current investigation points towards the role of naphthyl group in design of new inhibitors of melanogenesis and the antioxidants with improved efficacy. Communicated by Ramaswamy H. Sarma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07391102.2020.1857841DOI Listing
December 2020

Exploring natural products-based cancer therapeutics derived from egyptian flora.

J Ethnopharmacol 2021 Apr 25;269:113626. Epub 2020 Nov 25.

Natural Products Laboratory, IBL, Leiden University PO Box 9505, 2300RA, Leiden, the Netherlands.

Ethnopharmacological Relevance: Egyptian plants are a rich source of natural molecules, representing considerable biodiversity due to climate variations between the Northern, Southern, Eastern and Western regions of the country. Sinai is considered a precious nature reserves preserving flora, fauna, marine organisms, and historical habitats with ancient origins. Here, traditional medicinal approaches have been used for hundreds of years. Healthy lifestyles, low levels of stress and microbial infections, and a dependence on flora and herbal medicine might in combination explain why the burden of cancer is lower in some regions than in others.

Aim Of The Study: The primary aim of this review is to document the plants and natural products that are used as foods and medicines in Egypt, in general, and in Sinai, in particular, with a focus on those with demonstrated anticancer activities. The documented traditional uses of these plants are described, together with their chemical and pharmacological activities and the reported outcomes of clinical trials against cancer.

Materials And Methods: A literature search was performed to identify texts describing the medicinal plants that are cultivated and grown in Egypt, including information found in textbooks, published articles, the plant list website (http://www.theplantlist.org/), the medicinal plant names services website (http://mpns.kew.org/mpns-portal/), and web databases (PubMed, Science Direct, and Google Scholar).

Results And Discussion: We collected data for most of the plants cultivated or grown in Egypt that have been previously investigated for anticancer effects and reported their identified bioactive elements. Several plant species, belonging to different families and associated with 67 bioactive compounds, were investigated as potential anticancer agents (in vitro studies). The most potent cytotoxic activities were identified for the families Asteraceae, Lamiaceae, Chenopodiaceae, Apocynaceae, Asclepiadaceae, Euphorbiaceae, Gramineae, and Liliaceae. The anticancer activities of some species, such as Punica granatum L., Nerium oleander L., Olea europea L., Matricaria chamomilla L., Cassia acutifolia L., Nigella sativa L., Capsicum frutescens L., Withania somnifera L., and Zingiber officinale Roscoe, have been examined in clinical trials. Among the various Egyptian plant habitats, we found that most of these plants are grown in the North Sinai, New-Delta, and Giza Governorates.

Conclusion: In this review, we highlight the role played by Egyptian flora in current medicinal therapies and the possibility that these plants may be examined in further studies for the development of anticancer drugs. These bioactive plant extracts form the basis for the isolation of phytochemicals with demonstrated anticancer activities. Some active components derived from these plants have been applied to preclinical and clinical settings, including resveratrol, quercetin, isoquercetin, and rutin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2020.113626DOI Listing
April 2021

Natural isocoumarins: Structural styles and biological activities, the revelations carry on ….

Phytochemistry 2021 Jan 7;181:112568. Epub 2020 Nov 7.

College of Food and Biological Engineering, Jiangsu University, Zhenjiang, 212013, China; Al-Rayan Colleges, Medina, 42541, Saudi Arabia.

Isocoumarins and dihydroisocoumarins are lactonic phytochemicals plentiful in microbes and higher plants. These are an amazing small scaffolds consecrated with all types of pharmacological applications. Our previous review covered the period 2000-2016, documenting the then known natural products of this class; the current article is a critical account of discovery of known as well as undescribed structural types and pharmacological activities reported in the course of 2016-2020. The classification revealed in our previous review based on the biogenetic origin is further buttressed by discovery of new members of each class and some new structural types hitherto unknown have also been identified. Similarly, the biological activities and SAR conclusions identified were found to be valid as well, nonetheless with new accompaniments. The most recent available literature on the structural diversity and biological activity of these natural products has been included. The information documented in this article are collected from scientific journals, books, electronic search engines and scientific databases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phytochem.2020.112568DOI Listing
January 2021

Screening for natural and derived bio-active compounds in preclinical and clinical studies: One of the frontlines of fighting the coronaviruses pandemic.

Phytomedicine 2020 Aug 29:153311. Epub 2020 Aug 29.

Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, S-106 91, Stockholm, Sweden; Department of Chemistry, Faculty of Science, Menoufia University, 32512 Shebin El-Kom, Egypt; H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan; International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China. Electronic address:

Background: Starting December 2019, mankind faced an unprecedented enemy, the COVID-19 virus. The world convened in international efforts, experiences and technologies in order to fight the emerging pandemic. Isolation, hygiene measure, diagnosis, and treatment are the most efficient ways of prevention and intervention nowadays. The health organizations and global care systems screened the available resources and offered recommendations of approved and proposed medications. However, the search for a specific selective therapy or vaccine against COVID-19 remains a challenge.

Methods: A literature search was performed for the screening of natural and derived bio-active compounds which showed potent antiviral activity against coronaviruses using published articles, patents, clinical trials website (https://clinicaltrials.gov/) and web databases (PubMed, SCI Finder, Science Direct, and Google Scholar).

Results: Through the screening for natural products with antiviral activities against different types of the human coronavirus, extracts of Lycoris radiata (L'Hér.), Gentiana scabra Bunge, Dioscorea batatas Decne., Cassia tora L., Taxillus chinensis (DC.), Cibotium barometz L. and Echinacea purpurea L. showed a promising effect against SARS-CoV. Out of the listed compound Lycorine, emetine dihydrochloride hydrate, pristimerin, harmine, conessine, berbamine, 4`-hydroxychalcone, papaverine, mycophenolic acid, mycophenolate mofetil, monensin sodium, cycloheximide, oligomycin and valinomycin show potent activity against human coronaviruses. Additionally, it is worth noting that some compounds have already moved into clinical trials for their activity against COVID-19 including fingolimod, methylprednisolone, chloroquine, tetrandrine and tocilizumab.

Conclusion: Natural compounds and their derivatives could be used for developing potent therapeutics with significant activity against SARS-COV-2, providing a promising frontline in the fighting against COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phymed.2020.153311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455571PMC
August 2020

Synthesis of biphenyl oxazole derivatives via Suzuki coupling and biological evaluations as nucleotide pyrophosphatase/phosphodiesterase-1 and -3 inhibitors.

Eur J Med Chem 2020 Dec 23;208:112759. Epub 2020 Aug 23.

Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, 22060, Pakistan. Electronic address:

Oxazole derivatives are important medicinal compounds which are inhibitors of various enzymes such as NPP1, NPP2, NPP3, tyrosine kinase, dipeptidyl-peptidase IV, cyclooxygenase-2, and protein tyrosine phosphatase. In this study, an extensive range of new biologically active biphenyl oxazole derivatives was synthesized in high to excellent yields (57-93%) through Suzuki-Miyaura cross-coupling of bromophenyloxazole with different boronic acids. The reaction was carried out in wet toluene under mild conditions. Overexpression of nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) and NPP3 has been associated with various health disorders including chondrocalcinosis, cancer, osteoarthritis, and type 2 diabetes. We evaluated the inhibitory potential and selectivity of the synthesized compounds (3a-3q) towards NPP1 and NPP3 at 100 μM concentrations. We found two compounds that were selective and potent inhibitors of these two enzymes on the artificial substrate thymidine 5'-monophosphate para-nitrophenyl ester: compound 3n inhibited NPP1 with an IC of 0.15 μM, and compound 3f inhibited NPP3 with an IC value of 0.17 μM. The compounds with promising inhibitory potential were docked inside the proteins of NPP1 and NPP3 isozymes to get insight into the plausible binding interactions with active site residues.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmech.2020.112759DOI Listing
December 2020

Understanding the enzymatic inhibition of intestinal alkaline phosphatase by aminophenazone-derived aryl thioureas with aided computational molecular dynamics simulations: synthesis, characterization, SAR and kinetic profiling.

Mol Divers 2020 Aug 29. Epub 2020 Aug 29.

Department of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Pakistan.

The work presented in this paper aims toward the synthesis of aryl thiourea derivatives 4a-l of pyrazole based nonsteroidal anti-inflammatory drug named 4-aminophenazone, as potential inhibitors of intestinal alkaline phosphatase enzyme. The screening of synthesized target compounds 4a-l for unraveling the anti-inflammatory potential against calf intestinal alkaline phosphatase gives rise to lead member 4c possessing IC value 0.420 ± 0.012 µM, many folds better than reference standard used (KHPO IC = 2.8 ± 0.06 µM and L-phenylalanine IC = 100 ± 3.1 µM). SAR for unfolding the active site binding pocket interaction along with the mode of enzyme inhibition based on kinetic studies is carried out which showed non-competitive binding mode. The enzyme inhibition studies were further supplemented by molecular dynamic simulations for predicting the protein behavior against active inhibitors 4c and 4g during docking analysis. The preliminary toxicity of the synthesized compounds was determined by using brine shrimp assay. This work also includes detailed biochemical analysis along with RO5 parameters for all the newly synthesized drug derivatives 4a-l.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11030-020-10136-9DOI Listing
August 2020

A comparative study of synthetic approaches towards total synthesis of histrionicotoxin: a selective inhibitor of nicotinic acetylcholine receptors.

J Asian Nat Prod Res 2020 Aug 24:1-19. Epub 2020 Aug 24.

Department of Chemistry, Hazara University Mansehra, Mansehra 21120, Pakistan.

The aim of this review is to provide a critical and comparative account of the total synthetic approaches toward histrionicotoxins, alkaloids isolated from skin extracts of Colombian poison arrow frog . We have summarized the maneuvers in each paper by graphically detailing the synthesis and associated reaction niceties of only the key intermediates by different researchers. Fascinating structural feature of histrionicotoxins is "8-hydroxy-l-azaspiro[5.5]undecane core" with two side chains at C-2 and C-7 which differ in their length and nature of unsaturation. All synthetic approaches to histrionicotoxins aim at the construction of key intermediate "azaspiro[5.5]undecane ring" and installation of side chains at C-2 and C-7.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10286020.2020.1810670DOI Listing
August 2020

Anticancer Effects of Stilbene Derivatives: Mechanistic Studies on HeLa and MCF-7 Cells.

Anticancer Agents Med Chem 2021 ;21(6):793-802

Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad-22060, Pakistan.

Background And Objective: The growing prevalence of cancer and the resulting chemoresistance exert a huge burden on healthcare systems and impose a great challenge to public health around the world. In efforts to develop new chemotherapeutic agents for cancer treatment, a class of heterocyclic compounds i.e. triazine-based molecules were investigated as anticancer agents.

Materials And Methods: New triazine hybrids of stilbene were synthesized and evaluated as anticancer agents for cervical (HeLa) and breast (MCF-7) carcinoma cells. The compound (7e), sodium (E)-6,6'-(ethene-1,2- diyl)bis(3-((4-chloro-6-((3-luorophenyl)amino)-1,3,5-triazin-2-yl)amino)benzenesulfonate) was found to be most potent among synthesized derivatives and was explored further for detailed mechanistic studies.

Results: In a set comprised of twelve derivatives, compound 7e, sodium (E)-6,6'-(ethene-1,2-diyl)bis(3-((4- chloro-6-((3-luorophenyl)amino)-1,3,5-triazin-2-yl)amino)benzenesulfonate) was found most potent inhibitor for HeLa and MCF-7 cells.

Discussion: The present study has revealed that compound 7e may activate mitochondrial pathway of apoptosis in HeLa and MCF-7 cells which was assessed by DNA binding studies, estimation of the release of Lactate Dehydrogenase (LDH), fluorescence imaging, production of Reactive Oxygen Species (ROS) in cancer cells, analysis of cell cycle by flow cytometry, change in Mitochondrial Membrane Potential (MMP) and activation of caspase-9 and caspase-3.

Conclusion: Compound 7e may serve as a lead in designing new anticancer compounds based on stilbene scaffold.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1871520620666200811123230DOI Listing
January 2021

Synthesis, characterization, alkaline phosphatase inhibition assay and molecular modeling studies of 1-benzylidene-2-(4-tert- butylthiazol-2-yl) hydrazines.

J Biomol Struct Dyn 2020 Aug 11:1-14. Epub 2020 Aug 11.

Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, Pakistan.

Alkaline phosphatases are homodimeric protein enzymes which removes phosphates from several types of molecules. These catalyze the hydrolysis of monoesters in phosphoric acid which in turn catalyze a transphosphorylation reaction. Thiazoles are a privileged class of heterocyclic compounds which may potentially serve as effective phosphatase inhibitors. In this regard, the present research paper reports the facile synthesis and characterization of substituted 1-benzylidene-2-(4-tert-butylthiazol-2-yl) hydrazines with excellent yields. The synthesized compounds were tested for inhibitory potential against alkaline phosphatases. The compound 1-(4-Hydroxy, 3-methoxybenzylidene)-2-(4-tert-butylthiazol-2-yl) hydrazine ( was found to be the most potent inhibitor of human tissue non-alkaline phosphatase in this group of molecules with an IC value of 1.09 ± 0.18 µM. The compound 1-(3,4-dimethoxybenzylidene)-2-(4-tert-butylthiazol-2-yl) hydrazine exhibited selectivity and potency for human intestinal alkaline phosphatase with an IC value of 0.71 ± 0.02 µM. In addition, structure activity relationship and molecular docking studies were performed to evaluate their binding modes with the target site of alkaline phosphatase. The docking analysis revealed that the most active inhibitors showed the important interactions within the binding pockets of human intestinal alkaline phosphatase and human tissue non-alkaline phosphatase and may be responsible for the inhibitory activity of the compound towards the enzymes. Therefore, the screened thiazole derivatives provided an outstanding platform for further development of alkaline phosphatase inhibitors. Alkaline phosphatase assay revealed compound (1-(4-Hydroxy, 3-methoxybenzylidene)-2-(4-tert-butylthiazol-2-yl) hydrazine) as the most active inhibitor of with an IC value of 1.09 ± 0.18 µM. Computational evaluation clearly depicts several interactions within the binding pockets of and and maybe responsible for the inhibitory potential of the compound towards the enzymes. Highlights The synthesis of 1-(benzylidene) thiosemicarbazides was performed by reacting thiosemicarbazide with substituted aromatic aldehydes . The synthesized 1-(benzylidene) thiosemicarbazides was cyclized with 1-chloropinacolone to obtain the respective 1-benzylidene-2-(4-tert-butylthiazol-2-yl) hydrazines . The synthesized 1-benzylidene-2-(4-tert-butylthiazol-2-yl) hydrazines were successfully characterized using elemental analysis, FT-IR and multi nuclear NMR. Alkaline phosphatase assay and computational study was performed in favor of the synthesized 1-benzylidene-2-(4-tert-butylthiazol-2-yl) hydrazines .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07391102.2020.1802336DOI Listing
August 2020

Synthesis, computational studies and enzyme inhibitory kinetics of benzothiazole-linked thioureas as mushroom tyrosinase inhibitors.

J Biomol Struct Dyn 2020 Aug 7:1-9. Epub 2020 Aug 7.

College of Food and Biological Engineering, Jiangsu University, Zhenjiang, China.

Herein, we report synthesis of a set of benzothiazole-thiourea hybrids with aromatic and aliphatic side chains ( to ) using an elegant synthetic strategy. The newly synthesized benzothiazole-thiourea conjugates were subjected to In-vitro tyrosinase inhibition and free radical scavenging activity. Majority of the compounds indicated inhibition considerably improved than the standard; compound (Kojic acid with IC = 16.8320 ± 1.1600 µM) with IC = 1.3431 ± 0.0254 µM was found to be the best inhibitor. A non-competitive mode of inhibition of was disclosed with value of 2.8 µM. In order to study enzyme-inhibitor interactions SAR analysis molecular docking was carried out. The amino groups of thiourea were involved in hydrogen bonding with Glu322 showing the bond length of 1.74 and 2.70 Å, respectively. Moreover, the coupling of π-π was displayed between benzothiazole and benzene rings of His244 and His263, respectively. The outcome of this study might help to develop new inhibitors of melanogenesis, important for cosmetic and food products. Communicated by Ramaswamy H. Sarma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07391102.2020.1804459DOI Listing
August 2020

Synthesis, characterization, in vitro tissue-nonspecific alkaline phosphatase (TNAP) and intestinal alkaline phosphatase (IAP) inhibition studies and computational evaluation of novel thiazole derivatives.

Bioorg Chem 2020 09 12;102:104088. Epub 2020 Jul 12.

Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan. Electronic address:

Alkaline phosphatases (APs) are a class of homodimeric enzymes which physiologically possess the dephosphorylation ability. APs catalyzes the hydrolysis of monoesters into phosphoric acid which in turn catalyze a transphosphorylation reaction. Thiazoles are nitrogen and sulfur containing aromatic heterocycles considered as effective APs inhibitors. In this context, the current research paper presents the successful synthesis, spectroscopic characterization and in vitro alkaline phosphatase inhibitory potential of new thiazole derivatives. The structure activity relationship and molecular docking studies were performed to find out the binding modes of the screened compounds with the target site of tissue non-specific alkaline phosphatase (h-TNAP) as well as intestinal alkaline phosphatase (h-IAP). Compound 5e was found to be potent inhibitor of h-TNAP with IC value of 0.17 ± 0.01 µM. Additionally, compounds 5a and 5i were found to be highly selective toward h-TNAP with IC values of 0.25 ± 0.01 µM and 0.21 ± 0.02 µM, respectively. In case of h-IAP compound 5f was the most potent inhibitor with IC value of 1.33 ± 0.10 µM. The most active compounds were resort to molecular docking studies on h-TNAP and h-IAP to explore the possible binding interactions of enzyme-ligand complexes. Molecular dynamic simulations were carried out to investigate the overall stability of protein in apo and holo state.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2020.104088DOI Listing
September 2020

New Hybrid Scaffolds Based on Carbazole-Chalcones as Potent Anticancer Agents.

Anticancer Agents Med Chem 2020 Jul 20. Epub 2020 Jul 20.

Department of Chemistry and Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7DN. United Kingdom.

Background And Objectives: Despite various technological advances for the treatment of cancer, the identification of new chemical entities with potent anticancer effects remain an indispensable requirement of the time due to multi-drug resistance exhibited by previously developed anticancer drugs. Particularly, the hybrid drugs incorporating two individual bioactive pharmacophores present medicinally important structural leads, thus improving the pharmacodynamic profile of the drug molecules. The antiproliferative and pro-apoptotic activity of the carbazole-chalcone hybrids on human breast and cervical cancer cells will be examined.

Materials And Methods: To overcome such complications, in the current study, we evaluated the cytotoxic effects of carbazole-chalcone hybrids on human breast adenocarcinoma (MCF-7), cervical adenocarcinoma (HeLa) cells and normal cells i.e., baby hamster kidney cells (BHK-21) using MTT (dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide) assay. The mechanistic studies were performed on potent compound 4g by fluorescent microscopic studies, release of lactate dehydrogenase (LDH) and mitochondrial membrane potential, activation of caspase-9 and -3 and flow cytometric analysis.

Results: As revealed by MTT assay, compound 4g was identified as the most potent derivative among the tested series with IC50 values of 5.64 and 29.15 μM against HeLa and MCF-7 cells, respectively. The results were compared with cisplatin. Fluorescent microscopic studies using 4',6-diamidino-2-phenylindole (DAPI) and propidium iodide (PI) staining confirmed the occurrence of apoptosis in HeLa cells treated with the most active compound 4g. Moreover, compound 4g also triggered the release of lactate dehydrogenase (LDH) in treated HeLa and MCF-7 cells while a luminescence assay displayed a remarkable increase in the activity of caspase-9 and -3. Moreover, flow cytometric results revealed that compound 4g caused G0/G1 arrest in the treated HeLa cells.

Conclusion: Our results demonstrated that the compound 4g possesses chemotherapeutic properties against breast cancer and cervical adenocarcinoma cells, thus warranting further research to test the anticancer efficacy of this compound at clinical level.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1871520620666200721110732DOI Listing
July 2020

Bisthioureas of pimelic acid and 4-methylsalicylic acid derivatives as selective inhibitors of tissue-nonspecific alkaline phosphatase (TNAP) and intestinal alkaline phosphatase (IAP): Synthesis and molecular docking studies.

Bioorg Chem 2020 08 3;101:103996. Epub 2020 Jun 3.

Center for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan. Electronic address:

Alkaline phosphatases (ALPs) are membrane bound metalloenzymes, distributed all over the body. Recent studies have revealed that by targeting ALPs can lead towards the treatment of many deadliest diseases including cardiac, cancerous and brain diseases. Thioureas and their derivatives are of considerable significance and are privileged scaffolds in medicinal chemistry. They show a wide range of pharmacological activities such as antibacterial, antiparasitic, anti-inflammatory and antioxidants etc. On the other hand, salicylic acid and its derivatives are known for its broad spectrum of activities. The work presented comprises of synthesis of N-acyl-N'-aryl substituted bisthioureas of pimelic acid (1-7) and 3,5-dimethyl pyrazole (11), 1-aroyl-3-aryl thiourea (12) and 1,3,4-oxadiazole (13) derivatives of 4-methyl salicylic acid. Structures of all the synthesized compounds were characterized by FT-IR and H NMR spectroscopic analysis. Synthesized compounds were evaluated for their alkaline phosphatases inhibition potential and exhibited high potency as well as selectivity towards h-TNAP and h-IAP. Compound 7 and 12 which were the bisthiourea derivative of pimmelic acid and thiourea derivative of 4-methyl salicylic acid, respectively, showed excellent selectivity against h-TNAP and h-IAP, respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2020.103996DOI Listing
August 2020

Synthesis, bioactivity and binding energy calculations of novel 3-ethoxysalicylaldehyde based thiosemicarbazone derivatives.

Bioorg Chem 2020 07 12;100:103924. Epub 2020 May 12.

Institute of Marine Biotechnology, Universiti Malaysia Terengganu, 21030 Kuala Nerus, Terengganu, Malaysia.

In recent decade, the entrance of α-N-heterocyclic thiosemicarbazones derivates (Triapne, COTI-2 and DpC) in clinical trials for cancer and HIV-1 has vastly increased the interests of medicinal chemists towards this class of organic compounds. In the given study, a series of eighteen new (3a-r) 3-ethoxy salicylaldehyde-based thiosemicarbazones (TSC), bearing aryl and cycloalkyl substituents, were synthesized and assayed for their pharmacological potential against carbonic anhydrases (hCA I and hCA II), cholinesterases (AChE and BChE) and α-glycosidase. The hCA I isoform was inhibited by these novel 3-ethoxysalicylaldehyde thiosemicarbazone derivatives (3a-r) in low nanomolar levels, the Ki of which differed between 144.18 ± 26.74 and 454.92 ± 48.32 nM. Against the physiologically dominant isoform hCA II, the novel compounds demonstrated Ks varying from 110.54 ± 14.05 to 444.12 ± 36.08 nM. Also, these novel derivatives (3a-r) effectively inhibited AChE, with Ki values in the range of 385.38 ± 45.03 to 983.04 ± 104.64 nM. For BChE was obtained with Ki values in the range of 400.21 ± 35.68 to 1003.02 ± 154.27 nM. For α-glycosidase the most effective Ki values of 3l, 3n, and 3q were with Ki values of 12.85 ± 1.05, 16.03 ± 2.84, and 19.16 ± 2.66 nM, respectively. Moreover, the synthesized TCSs were simulated using force field methods whereas the binding energies of the selected compounds were estimated using MM-GBSA method. The findings indicate the present novel 3-ethoxy salicylaldehyde-based thiosemicarbazones to be excellent hits for pharmaceutical applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2020.103924DOI Listing
July 2020

New aryl Schiff bases of thiadiazole derivative of ibuprofen as DNA binders and potential anticancer drug candidates.

J Biomol Struct Dyn 2020 May 20:1-17. Epub 2020 May 20.

Healthcare Biotechnology Atta-ur-Rehman School of Applied Biosciences, National University of Science and Technology (NUST), Islamabad, Pakistan.

The work presented in this paper describes the synthesis of two new aryl Schiff bases [()--(4-(benzyloxy)-3-methoxybenzylidene)-5-(1-(4-isobutylphenyl)ethyl)-1,3,4-thiadiazol-2-amine] (ASB-1) and [()--(4-(benzyloxy)benzylidene)-5-(1-(4-isobutylphenyl)ethyl)-1,3,4-thiadiazol-2-amine] (ASB-2). These compounds were characterized by different analytical techniques and then studied for DNA binding. Binding studies were carried out at neutral pH (7.0) and at 37 °C by theoretical and experimental methods including DFT, molecular docking, spectroscopy (UV-visible, fluorescence), cyclic voltammetry (CV) and viscometry. Further investigations of these compounds were done on hepatocellular carcinoma; Huh-7 cancer cell line. Binding constant, free energy change and binding site size, i.e. K, ΔG and were evaluated which indicated that both ASB-1 and ASB-2 bind significantly and spontaneously with the DNA. However, data revealed relatively greater binding of ASB-1 with DNA. Spectral and voltammetric results were found supportive of each other. Binding site sizes and viscosity measurements verified the mixed binding mode of interactions as observed in molecular docking analysis, i.e. intercalation with groove binding. DNA binding studies were very well correlated with the studies performed on Huh-7 cell line as well as normal HEK-293 cell lines. The compound ASB-1 not only showed greater binding affinity toward DNA but also showed greater anticancer potency with least IC value as compared to ASB-2.[Formula: see text]HighlightsNew aryl Schiff bases of thiadiazole derivative of ibuprofen ASB-1 and ASB-2Reactivity and mixed binding mode of interaction with DNA by DFT and dockingGood agreements in the binding parameters by spectroscopy and voltammetryK, ΔG and determined greater for ASB-1indicating its stronger binding with DNAGreater anticancer potential of ASB-1against Huh-7 cell lineCommunicated by Ramaswamy H. Sarma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07391102.2020.1766569DOI Listing
May 2020

An efficient synthetic approach toward a sporadic heterocyclic scaffold: 1,3-Oxathiol-2-ylidenes; alkaline phosphatase inhibition and molecular docking studies.

Bioorg Med Chem Lett 2020 07 4;30(13):127238. Epub 2020 May 4.

Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan.

We developed a simple and robust method for synthesis of 1,3-oxathiol-2-ylidene benzamides (4a-m) a sporadic class of heterocycles, by reacting freshly prepared aroyl isothiocyanates, with ethyl 2-chloroacetoacetate in presence of N-methylimidazole in dry acetonitrile. The synthesized compounds were explored for their inhibition against alkaline phosphatases and HeLa cancer cell lines. The results suggest that almost all the compounds possess good % inhibition against both enzymes, with compound 4m showing dual inhibition while 4g and 4i as potent and selective inhibitors of TNAP and c-IAP respectively. Structure activity relationship for the active members of series has been carried out based on molecular docking studies. The result of SAR shows the involvement of active inhibitors in H-bonding at various sites with different amino acid residues in addition to secondary metal ion interactions with Zn ions inside the active pocket of the enzyme. The π-π interactions between the 1,3-oxathiole ring and imidazole ring of His321 and His 317 further defines the dual mode of inhibition by compound 4m. These compounds also possess inhibition potential against cervical cell lines in the range of 2.42-69.03% with the maximum inhibition shown by the unsubstituted member 4a compared to the reference drug cisplatin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmcl.2020.127238DOI Listing
July 2020

Synthesis, characterization, antimicrobial, antioxidant and computational evaluation of N-acyl-morpholine-4-carbothioamides.

Mol Divers 2020 Feb 25. Epub 2020 Feb 25.

Department of Biology, Laurentian University, 935 Ramsey Lake Road, Sudbury, ON, P3E 2C6, Canada.

The present research paper reports the convenient synthesis, successful characterization, in vitro antibacterial, antifungal, antioxidant potency and biocompatibility of N-acyl-morpholine-4-carbothioamides (5a-5j). The biocompatible derivatives were found to be highly active against the tested bacterial and fungal strains. Moreover, some of the screened N-acyl-morpholine-4-carbothioamides exhibited excellent antioxidant potential. Docking simulation provided additional information about possibilities of their inhibitory potential against RNA. It has been predicted by in silico investigation of the binding pattern that compounds 5a and 5j can serve as the potential surrogate for design of novel and potent antibacterial agents. The results for the in vitro bioassays were promising with the identification of compounds 5a and 5j as the lead and selective candidate for RNA inhibition. Results of the docking computations further ascertained the inhibitory potential of compound 5a. Based on the in silico studies, it can be suggested that compounds 5a and 5j can serve as a structural model for the design of antibacterial agents with better inhibitory potential. Binding mode of compound 5j inside the active site of RNA in 3D space. 5j displayed highest antibacterial potential than the reference drug ampicillin with ZOI 10.50 mm against Staphylococcus aureus. 5j also displayed highest antifungal potential than the reference drug amphotericin B with ZOI 18.20 mm against Fusarium solani.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11030-020-10054-wDOI Listing
February 2020

Hydrazine clubbed 1,3-thiazoles as potent urease inhibitors: design, synthesis and molecular docking studies.

Mol Divers 2020 Feb 24. Epub 2020 Feb 24.

Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, 22060, Pakistan.

Synthesis of a novel series of hydrazine clubbed 1,3-thiazoles (5a-m) has been described by reacting hydrazine-1-carbothioamides (3a-k) with α-chloro- or bromo-acetophenones (4a-d) in refluxing ethanol in good to excellent yields (65-86%). Structural confirmation was based upon spectroscopic techniques such as H-NMR, C-NMR, FT-IR and mass spectrometry. The biological application of these motifs has been demonstrated in terms of their strong urease inhibition activity. The results of in vitro study revealed that all the compounds are the potent inhibitors of urease. The IC (ranging in between 110 and 440 nM) values were higher as compared to that of standard, i.e., thiourea (IC = 490 ± 10 nM). The synthesized compounds were docked at the active sites of the Jack bean urease enzyme in order to explore the possible binding interactions of enzyme-ligand complexes; the results reinforced the in vitro biological activity results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11030-020-10057-7DOI Listing
February 2020

Donor-Pi-Acceptor Fluorene Conjugates, Based on Chalcone and Pyrimidine Derivatives: an Insight into Structure-Property Relationship, Photophysical and Electrochemical Properties.

J Fluoresc 2020 Mar 24;30(2):419-426. Epub 2020 Feb 24.

Center of Engineering Research, KFUPM, Dhahran, 31261, Kingdom of Saudi Arabia.

A small set of four new fluorenyl chromophores (5-5a-c) was accomplished by stepwise nucleophilic substitution, Friedel-Crafts acylation, Ullman coupling, aldol condensation and cyclization reactions. The fluorene moiety was substituted at 2,7,9 and 9' positions with diverse groups. The synthesized derivatives were characterized by FTIR, H-NMR and C-NMR spectroscopic techniques. The optical properties were evaluated by by UV-VIS absorption and Fluorescence studies. HOMO and LUMO energy levels were evaluated by electrochemical studies and were found at -5.37-5.83 eV and - 2.47-2.94 eV respectively with band gap energy values 2.88 to 2.91 eV. The band gap energy values suggested that these synthesized molecules can be manipulated in the designing of blue and green OLEDS. Graphical Abstract.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10895-020-02516-zDOI Listing
March 2020

Corrigendum to "Aroylthiourea derivatives of ciprofloxacin drug as DNA binder: Theoretical, spectroscopic and electrochemical studies along with cytotoxicity assessment" [Arch. Biochem. Biophys. 666 (2019) 83-98].

Arch Biochem Biophys 2020 06 27;686:108268. Epub 2020 Jan 27.

Healthcare Biotechnology Atta-ur-Rehman School of Applied Biosciences National University of Science and Technology (NUST), Islamabad, Pakistan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.abb.2020.108268DOI Listing
June 2020

Synthetic Approaches Towards Antihypercholesterolemic Drug Simvastatin.

Curr Org Synth 2019 ;16(5):652-670

Sulaiman Bin Abdullah Aba Al-Khail-Centre for Interdisciplinary Research in Basic Sciences (SA-CIRBS), International Islamic University, Islamabad 44000, Pakistan.

Cardiovascular diseases are among the most threatening problems being faced by twenty-first century humans. The core cause of these diseases is high cholesterol level. Simvastatin (1: Synvinolin) is a well-known cholesterol-lowering drug marketed under the trade name Zocor®, which significantly reduces the risk of cardiovascular diseases related to hypercholesterolemia and is effective in lowering the total plasma cholesterol, low-density and very low-density lipoprotein cholesterol. It also enhances the high-density lipoprotein cholesterol. This review article aims to provide an overview of several chemical and biological methods utilized for the production of simvastatin in high yields and purity. Many robust and scalable methods have been described using lovastatin (2: Mevinolin) as a starting material, produced by the fungal strain of Aspergelius terreus. Enzymatic synthesis of simvastatin is also highlighted in this review. In addition, detailed experimental conditions, as well as the compatibility for industrial-scale preparations of simvastatin are also discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1570179416666190725095951DOI Listing
July 2020

Novel N-Acyl-1H-imidazole-1-carbothioamides: Design, Synthesis, Biological and Computational Studies.

Chem Biodivers 2020 Mar 20;17(3):e1900509. Epub 2020 Feb 20.

Department of Biochemistry, Quaid-I-Azam University, Islamabad, 45320, Pakistan.

The present study reports the convenient synthesis, spectroscopic characterization, bio-assays and computational evaluation of a novel series of N-acyl-1H-imidazole-1-carbothioamides. The screened derivatives displayed excellent antioxidant activity, moderate antibacterial and antifungal potential. The screened derivatives were found to be highly biocompatible against hRBCs. Molecular docking ascertained the mechanism and mode of action towards the molecular target delineating that ligands and complexes were stabilized at the active site by electrostatic and hydrophobic forces in accordance to the corresponding experimental results. Docking simulation provided additional information about the possibilities of inhibitory potential of the compounds against RNA. Computational evaluation predicted that N-acyl-1H-imidazole-1-carbothioamides 5c and 5g can serve as potential surrogates for hit to lead generation and design of novel antioxidant and antibacterial agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cbdv.201900509DOI Listing
March 2020

Robust therapeutic potential of carbazole-triazine hybrids as a new class of urease inhibitors: A distinctive combination of nitrogen-containing heterocycles.

Bioorg Chem 2020 01 6;95:103479. Epub 2019 Dec 6.

School of Chemistry, The University of Manchester, Oxford Road, Manchester M13 9PL, United Kingdom; Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7DN, United Kingdom. Electronic address:

The inhibition of urease enzyme is very important as it plays a key role in the treatment of several urinary and gastrointestinal tract infections. This enzyme provides a suitable environment for Helicobacter pylori at the low pH of the stomach, a causative agent of gastric and peptic ulcer that may lead to cancer. In agriculture, the high urease content causes environmental and economic problems. In this pursuit, given the well-established importance of integrated pharmacophores in medicinal chemistry and to explore new inhibitors of urease featuring two distinct heterocyclic functionalities, we herein report a facile synthesis of carbazole-triazine hybrids (3a-j). These new propeller-shaped chemical scaffolds were evaluated for their urease inhibitory potential in order to identify suitable leads. The initial structure-activity survey work guided through in vitro bioactivity results recognized 3e and 3f as new starting point hits incorporating bulky iodo (3e) and strong electron-withdrawing nitro (3f) groups at the para-position of aryl amine component. The potent compounds (3e &3f) exhibited the highest activity with IC values of 5.6 and 6.7 µM, respectively. In the molecular docking analysis, these compounds depicted excellent binding interactions with the active site residues. The key interactions observed include hydrogen bonding, π-π interactions, π-cation and nickel atom coordination to the triazine nitrogen of both inhibitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2019.103479DOI Listing
January 2020

Synthesis, antibacterial activity and molecular docking study of vanillin derived 1,4-disubstituted 1,2,3-triazoles as inhibitors of bacterial DNA synthesis.

Heliyon 2019 Nov 19;5(11):e02812. Epub 2019 Nov 19.

Institute of Molecular Biology and Biotechnology, The University of Lahore, Defence Road Campus, Lahore, Pakistan.

Antimicrobial resistance (AMR) compelled scientists in general while pharmacists, chemists and biologists in specific to believe that we could always remain ahead of the pathogens. The pipeline of new drugs is running gasping and the inducements to develop new antimicrobials to address the global problems of drug resistance are weak. In this pursuit, effective endeavours to prepare new anti-bacterial entities is highly wished. The present study demonstrates successful synthesis of a library of 1,4-disbustituted 1,2,3-triazoles ( using Click-chemistry concept and anti-their bacterial potential. In this 1,3-dipolar cycloaddition, the 3-methoxy-4-(prop-2-yn-1-yloxy)benzaldehyde (1) was used as alkyne partner which was synthesized from vanillin and propargyl bromide and further reacted with differently substituted arylpropoxy azides () to furnish series of mono and 1,4-disubstituted-1,2,3-triazoles. All the synthesized compounds were characterized spectroscopically and were evaluated for their initial antimicrobial activity. Preliminary results of antibacterial screening revealed that the synthesized compounds have the highest inhibitory effects compare to the control ciprofloxacin. The compounds and were found to be the most active (MIC: 5 μg/mL, MIC: 10 μg/mL respectively) against various strains of gram-positive and gram-negative bacteria. The molecular docking study against 4GQQ protein with synthesized ligands was performed to see the necessary interactions responsible for anti-bacterial activity. The docking analysis of the most potent compound supported the antibacterial activity exhibiting high inhibition constant and binding energy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.heliyon.2019.e02812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872831PMC
November 2019