Pyrazole-Thiazole Hybrids: Synthesis and Biological Evaluation against <i>Trypanosoma cruzi</i> and <i> <i>Mycobacterium tuberculosis</i> </i>

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.