Aim: We report the synthesis and biological evaluation of a small library of 15 functionalized 3-styryl-2-pyrazolines and pyrazoles, derived from curcuminoids, as trypanosomicidal agents. Methods & results: The compounds were prepared via a cyclization reaction between the corresponding curcuminoids and the appropriate hydrazines. All of the derivatives synthesized were investigated for their trypanosomicidal activities. Compounds 4a and 4e showed significant activity against epimastigotes of Trypanosoma cruzi, with IC50 values of 5.0 and 4.2 μM, respectively, accompanied by no toxicity to noncancerous mammalian cells. Compound 6b was found to effectively inhibit T. cruzi triosephosphate isomerase. Conclusion: The up to 16-fold higher potency of these derivatives compared with their curcuminoid precursors makes them a promising new family of T. cruzi inhibitors.
Keywords: 4,5-dihydropyrazoles; Chagas disease; Trypanosoma cruzi; pyrazoles; pyrazolines; trypanosomicidal agents.