Synthesis, computational study, and antileishmanial and antifungal evaluation of phenoxyacetophenone hydrazones bearing a 4-arylthiazole moiety

Abstract

A series of new phenoxyacetophenone hydrazones 6a-l bearing a 4-arylthiazole moiety were synthesized and tested as antileishmanial agents. After spectroscopic and computational characterization of the synthesized compounds, their antileishmanial and antifungal activities were investigated in vitro. All compounds exhibited good antileishmanial activity, demonstrating IC50 values = 3.63–17.4 μg/ml against promastigotes of Leishmania major. Certainly, the para-tolyl analog 6b showed the most potent activity against promastigotes. Compounds 6b, 6c, 6f, and 6i-6k with good activity against promastigotes (IC50 values ≤ 7.59 μg/ml) were subjected to further bioassay on the amastigotes of L. major, as well as cytotoxicity evaluation against host-cell macrophages. The representative compounds displayed substantial anti-amastigote activity (IC50 values ≤ 21.3 μg/ml) with good selectivity index (SI > 18). Additionally, the in vitro antifungal screening against yeasts, molds and dermatophytic fungi revealed that several compounds had respectable activity against dermatophytes. These results demonstrate that the thiazolyl-hydrazones 6 are proper leads for further design and development of potential antileishmanial agents.