Synthesis and Evaluation of NH2 and SH Linker Free Benzothiazole-Triazole Compounds: Insights into Antimicrobial Efficacy

Objective: To evaluate the antimicrobial effectiveness of a novel 5-(1,3-benzothiazol-2-yl)-4-[(E)-(phenylmethylidene)amino]-4H-1,2,4-triazole-3-thiol derivatives. Methods: Starting from 2-aminothiophenol, a series of novel benzothiazole tethered triazole compounds were synthesized using conventional multi-step reactions. The reaction conditions were optimized for yield. Characterization was performed using ¹H, ¹³C NMR, IR, and mass spectrometry. To determine the antimicrobial activity, both the agar well diffusion method and micro broth dilution method were employed. Molecular docking was conducted with AutoDock Vina, and ADME analysis was performed using SwissADME. The evaluation of toxicity was carried out using ADMETlab 2.0. Results and Discussion: Compound with a 2-NO₂ substitution showed potent antibacterial activity against E. coli, with an inhibition of 50 µg/mL, similar to the standard drug chloramphenicol. The derivatives containing 3-Br and thiophene substitutions exhibited excellent activity against P. aeruginosa, with an inhibition concentration of 50 µg/mL. Moreover, the compounds with substitutions of 4-Br, 2,4-F, 4-F, and thiophene showed notable antifungal activity against C. albicans at a concentration of 250 µg/mL, surpassing the effectiveness of the standard drug griseofulvin. The results of molecular docking indicated that the compounds possessing 2-NO₂, 3-Br, and 2,4-F substitutions displayed the most potent binding affinities towards their target proteins. The ADMET properties of these compounds were thoroughly evaluated and confirmed their drug-like characteristics and pharmacokinetic viability. Conclusions: The results of the antimicrobial activity assays and molecular docking studies indicate that several of the synthesized compounds demonstrated potency equal to or exceeding that of standard drugs. Furthermore, the ADMET profiles of these compounds were favourable, suggesting good pharmacokinetic properties. These findings highlight the potential of the synthesized compounds as effective antimicrobial agents, warranting further investigation and development.