Abstract

In search of new active molecules, a small focused library of tetrazoloquinoline-based 1,2,3-triazoles has been efficiently prepared via click chemistry approach. Several derivatives were found to be exhibiting promising antimicrobial and antioxidant activity characterized by their lower minimum inhibitory concentration values. All the synthesized compounds exhibited excellent antibacterial activity against Gram negative bacteria E. coli and F. devorans and antifungal activity against C. albicans and A. niger. Further, these compounds were tested for their antitubercular activity against dormant MTB H37Ra and dormant M. bovis BCG using XRMA assay protocol and showed no significant activity. Also, the synthesized compounds were found to have potential antioxidant activity with IC₅₀ range = 12.48–50.20 μg/mL. Furthermore, to rationalize the observed biological activity data, the molecular docking study also been carried out against the active site of fungal C. albicans enzyme P450 cytochrome lanosterol 14α-demethylase, which revealed a significant correlation between the binding score and biological activity for these compounds. The results of the in vitro and in silico study suggest that the triazole-incorporated tetrazoloquinolines may possess the ideal structural requirements for further development of novel therapeutic agents.

摘要

为了寻找新的活性分子，通过点击化学方法有效地制备了一个基于四唑喹啉的 1,2,3-三唑的小型集中文库。发现几种衍生物表现出有希望的抗微生物和抗氧化活性，其特征是它们的最低抑制浓度值较低。所有合成的化合物对革兰氏阴性菌E.coli和F. devorans均表现出优异的抗菌活性，对C. albicans和A. niger具有抗真菌活性。此外，测试了这些化合物对休眠MTB H37Ra和休眠M. bovis BCG的抗结核活性使用 XRMA 测定方案，并没有显示出显着的活性。此外，发现合成的化合物具有潜在的抗氧化活性，IC ₅₀范围 = 12.48–50.20 μg/mL。此外，为了使观察到的生物活性数据合理化，还​​对真菌白色念珠菌酶 P450 细胞色素羊毛甾醇 14α-去甲基化酶的活性位点进行了分子对接研究，揭示了这些化合物的结合评分和生物活性之间的显着相关性. 体外和计算机研究的结果表明，掺入三唑的四唑并喹啉可能具有进一步开发新型治疗剂的理想结构要求。