Pyrazole-Thiazole Hybrids: Synthesis and Biological Evaluation against Trypanosoma cruzi and Mycobacterium tuberculosis.

Pyrazole-thiazole hybrids 1-(a-k) were synthesized and fully characterized to investigate their biological activities against Trypanosoma cruzi and Mycobacterium tuberculosis . Physicochemical profiling confirmed favorable drug-like properties across the series. Biological assays identified compound 1g (3-F) as the most active against T. cruzi, with IC50 values of 11.66 μM (SI > 42.8) in trypomastigotes and 26.83 μM (SI > 18.9) in amastigotes. Compound 1h (4-Br) displayed significant antimycobacterial activity, with a MIC of 32.28 μM against the H37Rv strain. In silico 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.