Abstract
Leishmaniasis affects millions of people in tropical and subtropical regions. Currently, only a few medications are available for its treatment, many of which cause adverse effects. Therefore, the development of effective, and safer drugs is urgently needed. Leishmania major Pteridine reductase-1 (LmPTR-1) is a vital enzyme for parasite survival, and thus serves as a valid drug target. Our investigation on the ethanolic extract of Tussilago farfara L. resulted in the isolation of twenty known phenolic compounds 1–20. Among them, vanillic acid (1), 1S,3R,4R,5R)-3,5-di-O-caffeoylquinic acid (14), and 3,4,5-tri-O-caffeoylquinic acid methyl ester (20) are first time reported here. Compounds (1S,3R,4S,5R)-3,5-di-O-caffeoylquinic acid (15), 3,4-di-O-caffeoylquinic acid (16), 4,5-di-O-caffeoylquinic acid (17), and 3,4-di-O-caffeoylquinic acid methyl ester (18) exhibited LmPTR-1 inhibition with IC50 between 81.9–189.7 μΜ. In silico studies further revealed strong interactions between compounds 15–18, and LmPTR-1 enzyme. In summary, quinic acid derivatives, containing caffeoyl moieties can serve as potential as anti-leishmanial agents.