Abstract

DESIGN, SYNTHESIS, AND ANTIMICROBIAL EVALUATION OF NOVEL ISATIN–MOXIFLOXACIN-BASED 1,2,3-TRIAZOLE DERIVATIVES

*Ms. Surabhi Sharma, Dr. Arun Kumar Patel, Dr. Aditya Sahu, Mr. Rishabh Kumar Sahu, Mr. Shivam Kurmi, Ms. Supriya Ojha

Abstract

The increasing emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis has created an urgent need for the development of new antimycobacterial agents with improved efficacy. In the present study, a series of six novel isatin–moxifloxacin-based 1H-1,2,3-triazole derivatives (6A–6F) were designed and synthesized by combining the pharmacologically important moxifloxacin and isatin scaffolds through a 1,2,3-triazole linker. The synthetic strategy involved three major steps: propargylation of moxifloxacin, preparation of substituted N-(2-azidoethyl)isatin intermediates, and copper-promoted azide–alkyne cycloaddition to afford the target conjugates. The synthesized compounds were characterized by physicochemical and spectroscopic techniques, including melting point determination, thin-layer chromatography (TLC), infrared spectroscopy (IR), and ^1H nuclear magnetic resonance (^1H NMR). The final derivatives were obtained in yields ranging from 53–72%, with melting points of 143–176 °C. The compounds were freely soluble in alcohol, soluble in acetone and dimethyl sulfoxide, and insoluble in water and benzene. Antifungal activity was evaluated by the agar diffusion method against Candida albicans and Aspergillus niger. Compound 6C showed the highest antifungal activity among the synthesized derivatives. Antitubercular activity was evaluated against M. tuberculosis H37Rv and clinical isolates resistant to streptomycin, isoniazid, rifampicin and ethambutol using the luciferase reporter phage assay. At 100 μg/mL, all six derivatives produced more than 50% reduction in relative light units against H37Rv, with compounds 6A and 6C showing more than 50% reduction against the resistant clinical isolates. The findings indicate that linking isatin and moxifloxacin through a 1,2,3-triazole scaffold provides promising compounds for further investigation as antimicrobial and antimycobacterial agents.

Keywords: Isatin; Moxifloxacin; 1,2,3-Triazole; Antimicrobial activity; Antifungal activity; Antitubercular activity; Mycobacterium tuberculosis; MDR-TB; Medicinal chemistry.