Hydrazones tethered disubstituted 1,2,3-triazoles: Design, synthesis, antitubercular and antimicrobial evaluation

A new series of hydrazones tethered 1,4-disubstituted 1,2,3-triazoles have been synthesized from novel N-substituted alkynes derived from benzohydrazides and benzyl bromides through Cu(I) catalyzed 1,3-dipolar cycloaddition reaction. All the newly synthesized triazoles were characterized by FTIR, H-1 NMR, C-13 NMR and HRMS. Further, the structure of one of the novel alkyne N'-benzylidene-N-(prop-2-yn-1-yl)benzohydrazide has been also characterized by single X-ray crystallography (CCDC 2192009 ). The synthesized compounds were assessed for antitubercular and antimicrobial activities. Isoniazid hydrazone tethered with disubstituted 1,2,3-triazole(7s), displayed moderate antimycobacterial activity. Compound 7r exhibited apperciable inhibition against bacterial strains-S. aureus, B. subtiils, E. coli and fungal strains-C. albicans and A. niger with MIC value 0.0121 mu mol/mL as compared to standard drugs used. Further, molecular docking studies of broadly active compounds 7r and 7s in the active site of DNA gyrase and Enoyl-acp reductase (INHA) respectively were also performed to have the probable mode of action. In-silico ADME study also reflects potential of synthesized triazoles as drug agent. (c) 2023 Elsevier B.V. All rights reserved.

Automated summary

A series of hydrazones tethered 1,4-disubstituted 1,2,3-triazoles were synthesized from novel N-substituted alkynes derived from benzohydrazides and benzyl bromides through Cu(I) catalyzed 1,3-dipolar cycloaddition reaction. The synthesized compounds were characterized by various spectroscopic techniques and the crystal structure of one compound was determined by X-ray crystallography. The compounds were evaluated for their antimicrobial and antitubercular activities, and two compounds showed promising results. Molecular docking studies and in-silico ADME studies were also conducted to understand the mode of action and the potential of the synthesized triazoles as drug agents.