In vitro and In silico evaluation of the Leishmanicidal and Trypanocidal activities of Lignan Methylpiperitol isolated from Persea Fulva

Abstract

Neglected Tropical Diseases are a significant concern as theyencompass various infections caused by pathogens prevalent intropical regions. The limited and often highly toxic treatmentoptions for these diseases necessitate the exploration of newtherapeutic candidates. In the present study, the lignanmethylpiperitol was isolated after several chromatographicsteps from Persea fulva L. E. Koop (Lauraceae) and its leishmani-cidal and trypanocidal activities were evaluated using in vitroand in silico approaches. The chemical structure of methylpiper-itol was defined by NMR and MS spectral data analysis. Theantiprotozoal activity of methylpiperitol was determined in vitroand indicated potency against trypomastigote forms of Trypa-nosoma cruzi (EC50 of 4.5 � 1.1 mM) and amastigote forms ofLeishmania infantum (EC50 of 4.1 � 0.5 mM), with no mammaliancytotoxicity against NCTC cells (CC50 > 200 mM). Moleculardocking studies were conducted using six T. cruzi and fourLeishmania. The results indicate that for the molecular targethypoxanthine phosphoribosyl transferase in T. cruzi and pite-ridine reductase 1 of L. infatum, the methylpiperitol obtainedbetter results than the crystallographic ligand. Therefore, thelignan methylpiperitol, isolated from P. fulva holds potential forthe development of new prototypes for the treatment ofNeglected Tropical Diseases, especially leishmaniasis.