Click chemistry in tuberculosis research: From drug design to therapeutic delivery - A systematic review

Zimo Ren; Paolo Coghi

doi:10.5155/eurjchem.16.1.83-96.2615

PDF

Published: Mar 31, 2025

DOI: https://doi.org/10.5155/eurjchem.16.1.83-96.2615

Keywords:

CuAAC, 1,2,3-Triazoles, Click chemistry, Drug discovery, Medicinal chemistry, Mycobacterium tuberculosis

Section

Review Article

Issue

Vol. 16 No. 1 (2025): March 2025

Dates

Received 2024-11-04
Accepted 2025-01-20
Published 2025-03-31

Zimo Ren

Department of Medical Division, School of Pharmacy, Macau University of Science and Technology, Macau, 999078, China

https://orcid.org/0009-0007-2534-444X

Paolo Coghi

Department of Medical Division, School of Pharmacy, Macau University of Science and Technology, Macau, 999078, China

https://orcid.org/0000-0002-0015-1453

Abstract

The molecular hybridization of 1,2,3-triazoles with various bioactive scaffolds has become a promising approach to the development of new antitubercular drugs, offering a versatile platform for improving drug efficacy and specificity. This review covers key advancements over the past decade in creating triazole-based hybrids that integrate azoles, coumarin/chromene, isoniazid, quinoline/dihydroquinoline, quinolone, ferrocene, isatin, furan, and other structures. These hybrid molecules generally show improved potency against both drug-sensitive and drug-resistant Mycobacterium tuberculosis strains while maintaining favorable toxicity profiles, making them particularly valuable in the current landscape of rising drug resistance. Structure-activity relationship (SAR) studies highlight that strategic substituent positioning and optimal linker selection are critical in enhancing antimycobacterial efficacy. Furthermore, modifications to the electronic and steric properties of the hybrids have been shown to influence their ability to bypass common resistance mechanisms, underscoring the potential of these compounds to overcome treatment barriers. In particular, several of these hybrids demonstrate promising activity against MDR-TB and XDR-TB strains, suggesting potential applications for immunocompromised patients, such as those with HIV co-infection. Collectively, these findings offer valuable insights for the rational design of next-generation antituberculosis agents that could transform tuberculosis (TB) treatment paradigms in both resistant and sensitive cases of TB.

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Ren, Z.; Coghi, P. Click Chemistry in Tuberculosis Research: From Drug Design to Therapeutic Delivery - A Systematic Review. Eur. J. Chem. 2025, 16, 83-96.

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