Antileishmanial and cytotoxic activity of dillapiole n-butyl ether

Abstract

ABSTRACT Among the neglected diseases, American cutaneous leishmaniasis (ACL) still remains highly endemic in some tropical regions. The currently available drugs for treatment are highly toxic, prompting the search for new therapeutic options. The aim of this study was to evaluate the toxic potential of dillapiole n-butyl ether (DBE) against Leishmania amazonensis and L. guyanensis, as well as its toxicity on human peripheral blood mononuclear cells (PBMCs) in vitro. For cell cytotoxicity, concentrations of DBE that ranged from 7.8 to 500 µM were used for 48 and 72 h. For the evaluation of the antileishmanial activity, DBE was tested at concentrations of 0.28 to 18 µM for 24, 48, and 72 h. A value of 36 µM was used for the amastigote assay. The selectivity index (SI) was determined by dividing the CC50/IC50 (macrophages/promastigotes). DBE exhibited a CC50 of 203.9 ± 0.5 µM in 72 h. DBE inhibited promastigote forms with an IC50 of 3.0 µM for both Leishmania species for 72 h. The standard, Pentacarinat®, showed an IC50 of 2.9 µM and 0.3 µM, respectively. The SI of DBE for both species was 67.9 for 72 h. DBE inhibited intracellular forms of L. amazonensis by 65.5% after 48 h. In molecular modeling, DLpOl-F showed two hydrogen bonds (SER418 and 421). DBE demonstrated promising in vitro antileishmanial potential.

Keywords

• Leishmania
• dillapiole analog
• semi-synthesis
• molecular modeling