背景:在持续的对抗细菌对抗生素的耐药性的斗争中,这项研究的重点是合成和评估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有前途的候选药物,具有广泛的治疗作用,包括疼痛缓解,防腐剂,抗菌,抗氧化剂,抗脲酶,抗炎,利尿剂,抗癌,抗惊厥药,抗糖尿病药,和抗偏头痛特性。
方法:使用其理化性质和光谱技术鉴定了所有合成化合物的结构,如IR和NMR。然后在体外抗微生物活性的分子对接研究中评估这些化合物,并进一步得到分子动力学研究的支持。
结果:化合物7,具有苯环上的6-氯基团,与标准抗生素环丙沙星相比,对革兰氏阳性金黄色葡萄球菌最有效。对接研究显示,所有10个配体的亲和力都很高且相当,化合物4和6对青霉素酰化酶突变体显示出最佳的对接活性。Further,在100nsMD模拟过程中,化合物6和10对鼠疫耶尔森氏菌的D-丙氨酸-D-丙氨酸连接酶(DDL)显示出显着的亲和力。
结论:值得注意的是,化合物7与5C1P蛋白的结合得分最高,这表明其作为开发有效和更安全的抗微生物剂的先导分子的潜力。这项研究为解决细菌耐药性不断升级的挑战提供了有价值的见解。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.