In Silico Molecular Docking and Molecular Dynamics Analysis of Antimicrobial Triazole Derivatives: Insights from Synthesis, Computational and In Vitro Studies.

IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS
Shikha Sharma, Naveen Kumawat, Suraj N Mali, Monika Meghani, Nitin Kumar, Bijo Mathew, Sunil Kumar
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Abstract

Introduction: In the ongoing fight against bacterial resistance to antibiotics, this study focuses on synthesizing and evaluating 1,2,4-triazole derivatives to explore their potential as new antibacterial agents. 1,2,4-Triazole compounds are promising drug candidates with a wide range of therapeutic effects, including pain relief, antiseptic, antimicrobial, antioxidant, antiurease, anti-inflammatory, diuretic, anticancer, anticonvulsant, antidiabetic, and antimigraine properties.

Method: The structures of all the synthesized compounds were identified using their physicochemical properties and spectral techniques, such as IR and NMR. These compounds were then evaluated in molecular docking studies against antimicrobial activity in vitro and further supported by molecular dynamics studies.

Result: Compound 7, featuring a 6-chloro group on the phenyl ring, emerged as the most effective against Gram-positive S. aureus compared to the standard antibiotic ciprofloxacin. Docking studies revealed high and comparable affinities for all ten ligands, with compounds 4 and 6 showing the best-docked activity against Penicillin Acylase mutants. Further, compounds 6 and 10 displayed significant affinity against D-alanine-D-alanine ligase (DDL) from Yersinia pestis during 100 ns MD simulation.

Conclusion: Notably, compound 7 demonstrated the highest binding score to the 5C1P protein, suggesting its potential as a lead molecule for the development of potent and safer antimicrobial agents. This research contributes valuable insights into addressing the escalating challenge of bacterial resistance.

抗菌三唑衍生物的分子对接和分子动力学分析:合成、计算和体外研究的启示。
简介:为了对抗细菌对抗生素的耐药性,本研究重点合成并评估了 1,2,4-三唑衍生物,以探索其作为新型抗菌剂的潜力。1,2,4-三唑化合物是很有前途的候选药物,具有广泛的治疗作用,包括止痛、防腐、抗菌、抗氧化、抗尿素酶、抗炎、利尿、抗癌、抗惊厥、抗糖尿病和抗偏头痛等特性:方法:利用理化性质和光谱技术(如红外光谱和核磁共振)确定所有合成化合物的结构。然后在分子对接研究中对这些化合物的体外抗菌活性进行了评估,并通过分子动力学研究进一步证实了这些化合物的抗菌活性:结果:与标准抗生素环丙沙星相比,苯环上带有 6 个氯基的化合物 7 对革兰氏阳性金黄色葡萄球菌最有效。对接研究显示,所有十种配体都具有很高的亲和力,其中化合物 4 和 6 对青霉素酰化酶突变体的对接活性最好。此外,在 100 ns MD 模拟过程中,化合物 6 和 10 对鼠疫耶尔森菌的 D-丙氨酸-D-丙氨酸连接酶(DDL)具有显著的亲和力:值得注意的是,化合物 7 与 5C1P 蛋白的结合得分最高,这表明它有可能成为开发强效、更安全的抗菌剂的先导分子。这项研究为应对不断升级的细菌耐药性挑战提供了宝贵的见解。
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来源期刊
CiteScore
3.10
自引率
5.60%
发文量
327
审稿时长
7.5 months
期刊介绍: Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews/mini-reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal: Target identification and validation Assay design, development, miniaturization and comparison High throughput/high content/in silico screening and associated technologies Label-free detection technologies and applications Stem cell technologies Biomarkers ADMET/PK/PD methodologies and screening Probe discovery and development, hit to lead optimization Combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries) Chemical library design and chemical diversity Chemo/bio-informatics, data mining Compound management Pharmacognosy Natural Products Research (Chemistry, Biology and Pharmacology of Natural Products) Natural Product Analytical Studies Bipharmaceutical studies of Natural products Drug repurposing Data management and statistical analysis Laboratory automation, robotics, microfluidics, signal detection technologies Current & Future Institutional Research Profile Technology transfer, legal and licensing issues Patents.
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