TB Research

Pyrazole-Thiazole Hybrids: Synthesis and Biological Evaluation againstand.

Cynthia Nathália Pereira, Lorraine Martins Rocha Orlando, Edinaldo Castro de Oliveira, Mirian Claudia de Souza Pereira, Christian S Canales Carnero, Oswaldo Julio Ramirez Delgado, Cesar Augusto Roque-Borda, Fernando Rogério Pavan, et al. (9 authors)

ACS omega · 2026-04

Abstract

Pyrazole-thiazole hybridswere synthesized and fully characterized to investigate their biological activities againstand. Physicochemical profiling confirmed favorable drug-like properties across the series. Biological assays identified compound(3-F) as the most active against, with ICvalues of 11.66 μM (SI > 42.8) in trypomastigotes and 26.83 μM (SI > 18.9) in amastigotes. Compound(4-Br) displayed significant antimycobacterial activity, with a MIC of 32.28 μM against the H37Rv strain.analyses suggested preferential stabilization of halogenated derivatives through hydrophobic and π-driven interactions in structurally related enzymatic pockets, used here as an exploratory model. Taken together, these findings demonstrate that halogen substitution strongly modulates affinity and biological performance, supporting pyrazole-thiazole hybrids as promising scaffolds for further optimization against neglected-parasite pathogens. Future studies expanding halogen patterns and probing alternative binding pockets may improve potency and target selectivity across this chemical space.