这项研究介绍了一系列来自萘啶酸的新型烷基硫基-1,2,4-三唑(4a-p)和巯基-1,2,4-三唑(3a-d)化合物。合成是精简的,涉及萘啶酸酰肼和各种异硫氰酸酯之间的相互作用,以产生环状和烷基(芳基)硫化物化合物,用1HNMR表征,13CNMR,IR,和元素分析。抗氧化能力通过DPPH和ABTS测定进行定量,突出了巨大的潜力,特别是对于复合3d,证明ABTSIC50值为0.397μM,与抗坏血酸相当(IC50=0.87μM)。通过对广谱革兰氏阳性和革兰氏阴性细菌的MIC评估,建立了抗菌功效。包括白色念珠菌.化合物3b,4e,4h,4j,4i,4m,4o显示广谱活性,4k和4m对大肠杆菌表现出明显的效力。分子对接研究验证了抗菌潜力,化合物4f和4h显示出高结合亲和力(对接评分为-9.8和-9.6kcal/mol,分别),表明与细菌酶靶标的强大相互作用。这些分数强调了化合物抗菌作用的机理基础,并支持其治疗前景。此外,化合物3b,4i,4m,通过药物相似性和毒性预测确定,突出了他们的有利形象,表明它们适合口服抗生素治疗。这项全面的研究,混合合成,在体外,和硅方法,强调三唑衍生物作为未来候选抗生素和抗氧化剂应用的潜力,特别是聚光灯化合物3b,4i,和4m,因为它们有希望的疗效和安全性。
This study introduces a series of novel Alkyl thio-1,2,4-triazole (4a-p) and mercapto-1,2,4-triazole (3a-d) compounds derived from nalidixic acid. The synthesis was streamlined, involving interactions between nalidixic acid hydrazide and various isothiocyanates to yield cyclic and alkyl(aryl) sulfide compounds, characterized using 1H NMR, 13C NMR, IR, and elemental analysis. Antioxidant capabilities were quantified through DPPH and ABTS assays, highlighting significant potential, especially for compound 3d, which demonstrated an ABTS IC50 value of 0.397 μM, on par with ascorbic acid (IC50 = 0.87 μM). Antibacterial efficacy was established through MIC assessments against a broad spectrum of Gram-positive and Gram-negative bacteria, including Candida albicans. Compounds 3b, 4e, 4h, 4j, 4i, 4m, and 4o showed broad-spectrum activity, with 4k and 4m exhibiting pronounced potency against E. coli. Molecular docking studies validated the antibacterial potential, with compounds 4f and 4h showing high binding affinities (docking scores of -9.8 and -9.6 kcal/mol, respectively), indicating robust interactions with the bacterial enzyme targets. These scores underscore the compounds\' mechanistic basis for their antibacterial action and support their therapeutic promise. Furthermore, compounds 3b, 4i, and 4m, identified through drug-likeness and toxicity predictions, were highlighted for their favorable profiles, suggesting their suitability for oral antibiotic therapies. This comprehensive study, blending synthetic, in vitro, and in silico approaches, emphasizes the triazole derivatives\' potential as future candidates for antibiotic and antioxidant applications, particularly spotlighting compounds 3b, 4i, and 4m due to their promising efficacy and safety profiles.