Anti-leishmanial potential of Betula utilis D. Don ethanolic extract, isolated betulin and its ester derivative on THP-1cells against Leishmania donovani

The aim of the present study was to evaluate the anti-leishmanial activity of Betula utilis D. Don ethanolic extract, isolated betulin (VA1), and its semisynthetic derivative (VA2) against Leishmania donovani. The ethanolic extract was obtained by Soxhlet extraction, and betulin was isolated by column chromatography. In-silico studies identified potential interaction sites between amphotericin B (standard drug), betulin, its semisynthetic derivative, and the active sites of pteridine reductase 1. VA2 exhibited important interactions with amino acid residues compared to betulin. Anti-promastigote activity and cytotoxicity tests were conducted using the (3-(4,5- dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide) cell viability method on modified THP-1 cells infected with L. donovani. Promastigotes were treated with varying concentrations of VA1, VA2, and Betula utilis ethanolic extract (EEBU) for 72 hours. In-vitro studies showed that EEBU, VA1, and VA2 significantly reduced viable L. donovani promastigotes, with IC50 values of (58.26 μM) EEBU, (58.39μM) VA1, and (25.50 μM) VA2. They also inhibited amastigote forms with low macrophage cytotoxicity. The significant anti-leishmanial activity exhibited by VA2 suggested it could serve as a lead agent against leishmaniasis.