Pyrrolidine-based 3-deoxysphingosylphosphorylcholine analogs as possible candidates against neglected tropical diseases (NTDs): identification of hit compounds towards development of potential treatment of <i>Leishmania donovani</i>

A rational-based process was adopted for repurposing pyrrolidine-based 3-deoxysphingosylphosphorylcholine analogs bearing variable acyl chains, different stereochemical configuration and/or positional relationships. Structural features were highly influential on activity. Amongst, enantiomer 1e having 1,2-vicinal relationship the -CH2O- and N-acyl moieties, a saturated palmitoyl chain an opposite to natural sphingolipids most potent hit compound against promastigotes showing IC50 value of 28.32 µM. The corresponding 1a 2-fold less eudismic ratio 0.54 in promastigotes. Compounds inhibited growth amastigotes more potently relative as selective safer. In silico docking study using homology model Leishmania donovani inositol phosphoceramide synthase (IPCS) provided plausible reasoning molecular factors underlying found Collectively, this suggests compounds potential further development new antileishmanial agents.