Molecular modeling and biological investigation of novel s-triazine linked benzothiazole and coumarin hybrids as antimicrobial and antimycobacterial agents

Journal of Biomolecular Structure and Dynamics, Journal Year: 2023, Volume and Issue: 42(7), P. 3814 - 3825

Published: May 22, 2023

AbstractAbstractA novel series of s-triazine linked benzothiazole and coumarin hybrids (6a-6d, 7a-7d, 8a-8d) were synthesized characterized by IR, NMR, mass spectrometry. The compound's in vitro antibacterial antimycobacterial activities also evaluated. Remarkable activity with MIC the range 12.5–62.5 μM antifungal 100–200 demonstrated antimicrobial analysis. Compounds 6b, 6d, 7b, 7d, 8a strongly inhibited all bacterial strains, while 6c, 7d had good to moderate efficacy against M. tuberculosis H37Rv. Synthesized are observed active pocket S. aureus dihydropteroate synthetase enzyme, according a molecular docking investigations. Among docked compounds, 6d strong interaction greater binding affinity, dynamic stability protein-ligand complexes was examined using simulation various settings at 100 ns. proposed compounds successfully maintained their structural integrity inside synthase, MD These silico analyses supported results compound which outstanding strains. In quest for new drug-like molecules, have been identified as promising lead compounds.Communicated Ramaswamy H. SarmaKeywords: 1,3,5-triazinebenzothiazolecoumarinbiological activityMD AcknowledgmentsThe authors thank IISc, Bangalore, India, CUG, Gujarat, providing spectral data. Department Chemistry Sardar Vallabhbhai National Institute Technology, Surat, facilities research work.Disclosure statementNo potential conflict interest reported authors.CRediT authorship contribution statementAjayrajsinh R. Zala: Conceptualization, methodology, writing original draft editing; Dinesh Kumar, Uvais Razakhan: Methodology; Dhanji P. Rajani: Biological Analysis; Iqrar Ahmad: review; Harun Patel: Writing-review Premlata Kumari: Supervision, Writing-review, editing.Additional informationFundingThe author(s) there is no funding associated work featured this article.

Language: Английский

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Halogenated class of oximes as a new class of monoamine oxidase-B inhibitors for the treatment of Parkinson’s disease: Synthesis, biochemistry, and molecular dynamics study

Computational Biology and Chemistry, Journal Year: 2023, Volume and Issue: 105, P. 107899 - 107899

Published: June 1, 2023

Language: Английский

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Novel coumarin benzamides as potent and reversible monoamine oxidase-B inhibitors: Design, synthesis, and neuroprotective effects

Bioorganic Chemistry, Journal Year: 2023, Volume and Issue: 142, P. 106939 - 106939

Published: Oct. 27, 2023

Language: Английский

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Exploration of a new class of monoamine oxidase B inhibitors by assembling benzyloxy pharmacophore on halogenated chalcones

Chemical Biology & Drug Design, Journal Year: 2023, Volume and Issue: 102(2), P. 271 - 284

Published: April 3, 2023

Eight derivatives of benzyloxy-derived halogenated chalcones (BB1-BB8) were synthesized and tested for their ability to inhibit monoamine oxidases (MAOs). MAO-A was less efficiently inhibited by all compounds than MAO-B. Additionally, the majority displayed significant MAO-B inhibitory activities at 1 μM with residual 50%. With an IC50 value 0.062 μM, compound BB4 most effective in inhibiting MAO-B, followed BB2 (IC50 = 0.093 μM). The lead molecules showed good activity reference inhibitors (Lazabemide 0.11 Pargyline 0.14). high selectivity index (SI) values observed (430.108 645.161, respectively). Kinetics reversibility experiments revealed that reversible competitive Ki 0.030 ± 0.014 0.011 0.005 respectively. Swiss target prediction confirmed probability targets both compounds. Hypothetical binding mode or is similarly oriented cavity Based on modelling results, a stable confirmation during dynamic simulation. From these it concluded potent selective they can be considered drug candidates treating related neurodegenerative diseases such as Parkinson's disease.

Language: Английский

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Inhibition of monoamine oxidases by benzimidazole chalcone derivatives

Applied Biological Chemistry, Journal Year: 2023, Volume and Issue: 66(1)

Published: June 17, 2023

Abstract Ten benzimidazole chalcone derivatives were synthesized, and their monoamine oxidase (MAO) inhibitory activity was evaluated. Most compounds showed higher against MAO-B than MAO-A. Compound BCH2 exhibited an IC 50 value of 0.80 μM, thereby showing the most potent inhibition amongst all. In addition, highest selectivity index (SI) with SI 44.11 compared to Among substituents, halogen group best inhibition, ortho -position B ring better para -site. comparison -substituents, increased in order, -Cl > -Br -F -H. found be a competitive inhibitor enzyme optimum kinetics, where K i 0.25 ± 0.014 μM. reversibility experiment, recovery pattern after similar that lazabemide. Thus, is potent, reversible, selective has been suggested as candidate for treatment neurological disorders.

Language: Английский

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Synthesis, molecular docking, molecular dynamic simulation studies, and anti-tubercular activity evaluation of substituted benzimidazole derivatives

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: July 13, 2023

Abstract Tuberculosis, colloquially referred to as TB, is a highly prevalent bacterial infection that persists substantial global health concern. The present article centers its attention on the comprehensive exploration of synthesis, molecular docking, and dynamic simulation investigations pertaining substituted benzimidazole derivatives. Additionally, meticulous assessment their anti-TB activities conducted. A series twelve derivatives ( 1–12 ) were successfully synthesized, employing scaffold consisting electron-withdrawing electron-donating groups. newly synthesized compounds defined by FT-IR, 1H-NMR, Mass spectra. Microplate Alamar Blue Assay (MABA) was used evaluate anti-mycobacterial activity compound against Mycobacterium tuberculosis (Mtb). Compounds 7 (MIC = 0.8 g/ml) 8 demonstrated exceptional potential inhibit M. compared standard (Isoniazid). In addition, docked with Mtb KasA protein (PDB ID: 6P9K), results docking confirmed experimental results, exhibited highest binding energy -7.36 − 7.17 kcal/mol, respectively. Both substances safe for acute inhalation cutaneous sensitization. These two have be potent inhibitors.

Language: Английский

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A reverse docking approach to explore the anticancer potency of natural compounds by interfering metastasis and angiogenesis

Journal of Biomolecular Structure and Dynamics, Journal Year: 2023, Volume and Issue: 42(14), P. 7174 - 7189

Published: Aug. 1, 2023

Angiogenesis, which results in the formation of new blood and lymph vessels, is required to serve metastatic cancer progression. Cancer medications may target these two interconnected pathways. Phytocompounds have emerged as promising options for treating cancer. In this study, we used a reverse docking strategy find candidate molecules treatment that both Following literature important cancer-causing proteins vascular endothelial growth factor D (VEGF-D) basic fibroblast (bFGF) angiogenesis matrix metalloproteinase-2 (MMP-2) metalloproteinase-9 (MMP-9) pathway were targeted. Protein Data Bank was retrieve structures chosen proteins. 22 significant plant metabolites identified having anticancer activity. To determine protein binding residues, active site prediction used. Using Lenvatinib Withaferin A reference ligands, affinity certain determined by analysis. Homoharringtonine viniferin, higher affinities when compared with scores -180.96 -180.36 against MMP-9, respectively. Moreover, Viniferin showed highest MMP-9 MMP-2 proteins, then subjected 100-ns molecular dynamic simulation. where they found be significantly stable. pharmacoinformatics investigations, majority our compounds non-toxic host. suggested natural substances cutting-edge treatments metastasis, aid accelerating drug development identifying viable therapeutic candidates.Communicated Ramaswamy H. Sarma.

Language: Английский

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Unearthing Nature's Defenders: A Computational Quest to Harness Plant Metabolites against the White Spot Syndrome Virus (WSSV) of Shrimp

Genetics of Aquatic Organisms, Journal Year: 2024, Volume and Issue: 8(1)

Published: April 30, 2024

This study addresses the global threat posed by White spot syndrome virus (WSSV) to aquaculture sector, causing substantial economic losses and impacting food security. The research explores a novel strategy using plant metabolites with proven antiviral properties as an eco-friendly alternative traditional chemical treatments. Employing molecular docking several bioinformatics tools, 63 are screened for their potential inhibit WSSV. Hyperoside, Quercetin, Rutin emerge top candidates, demonstrating highest binding affinities crucial viral proteins. investigation focuses interactions between these WSSV, identifying sites drug surface hotspots. Biological property analysis confirms suitability of compounds WSSV inhibitors without adverse effects. not only offers promising environmentally friendly approach combat but also contributes valuable insights into natural product-based therapies in aquaculture. By unveiling metabolites, this lays foundation innovative strategies protect mitigate diseases diverse settings. Further experimental verification through vitro vivo studies is strongly recommended validate encouraging findings.

Language: Английский

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Inhibition of Monoamine Oxidases by Pyridazinobenzylpiperidine Derivatives

Molecules, Journal Year: 2024, Volume and Issue: 29(13), P. 3097 - 3097

Published: June 28, 2024

Monoamine oxidase inhibitors (MAOIs) have been crucial in the search for anti-neurodegenerative medications and continued to be a vital source of molecular mechanistic diversity. Therefore, selective MAOIs is one main areas current drug development. To increase effectiveness safety treating Parkinson’s disease, new scaffolds reversible MAO-B are being developed. A total 24 pyridazinobenzylpiperidine derivatives were synthesized evaluated MAO. Most compounds showed higher inhibition than MAO-A. Compound S5 most potently inhibited with an IC50 value 0.203 μM, followed by S16 (IC50 = 0.979 μM). In contrast, all weak MAO-A inhibition. Among them, S15 3.691 3.857 had highest selectivity index (SI) 19.04 compared (3-Cl) greater other substituents -Cl > -OCH3 -F -CN -CH3 -Br at 3-position. However, 2- 4-position low inhibition, except (2-CN). addition, containing two or more exhibited kinetic study, Ki values 0.155 ± 0.050 0.721 0.074 respectively, competitive reversible-type Additionally, PAMPA, both lead demonstrated blood–brain barrier penetration. Furthermore, stability was 2V5Z-S5 complex pi–pi stacking Tyr398 Tyr326. These results suggest that potent, reversible, can used as potential agents treatment neurological disorders.

Language: Английский

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Effect of halogens on 3-[4-(dimethylamino) phenyl]-1-phenylprop-2-en-1-ones: development of a new class of monoamine oxidase-B inhibitors

Applied Biological Chemistry, Journal Year: 2024, Volume and Issue: 67(1)

Published: Aug. 23, 2024

Abstract Five dimethylamino-based chalcone derivatives (AC) were synthesized and evaluated for their inhibition degree against monoamine oxidase (MAO) enzymes. All AC compounds showed better inhibitory activity MAO-B than that MAO-A. AC4 the highest ability with an IC 50 value of 0.020 µM, similar to a reference drug safinamide (IC = 0.019 µM) MAO-B, followed by AC1 0.068 AC3 0.083 µM). Substituent -F in ring A (AC4) increased inhibition, -H (AC1), -Br (AC3), -Cl (AC2). The selectivity index (SI) was high (SI 82.00) as well other (44.41 98.15). found be reversible inhibitor confirmed through analysis using dialysis method. Interestingly, observed noncompetitive rare case K i values 0.011 ± 0.0036 µM. These experiments is potent selective MAO-B. Molecular docking revealed score (-9.510 kcal/mol). study molecular dynamics modeling protein–ligand complex more stable. It non-cytotoxic L929 cell line. In conclusion, compound shows promise inhibitor.

Language: Английский

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