Screening of Medicinal Plants Unraveled the Leishmanicidal Credibility of ; Highlighting Norcowanin, a Novel Anti-leishmanial Phytochemical Through In-silico Study

Leishmaniasis, one of the most prevalent yet neglected parasitic causes of death, yearns for therapeutic control and treatment. Severely toxic and inefficient modern-day pentavalent antimonials, caters the search for naturally derived drugs, as efficient alternatives for disease treatment. The anti-promastigote activity of ten different plants selected for their ethnomedicinal properties revealed significant leishmanicidal capacity; the most potent being methanolic extract with an IC value of 21.4 µg/ml. a plant endemic to North-Eastern India that is of the Clusiaceae family, is replete with such medicinal qualities as antimicrobial, antiviral, antiparasitic, and antiproliferative activities. Computational biology with its tools such as molecular docking has opened new horizons aimed at a better understanding of biological systems, complexes, and their interactions, and subsequently drug discovery via in silico techniques. Therefore, an study was designed to evaluate the binding capability of six phytochemicals- cowanin, cowanol, cowaxanthone, norcowanin, rubraxanthone, and a basic xanthone, found in against Pentamidine, a synthetic anti-leishmanial drug. The active sites of three characteristic enzymes belonging to the parasite: O-acetylserine sulfhydrylase (OASS), Trypanothione reductase (TryR), and N-Myristoyltransferase (NMT) were chosen as target proteins. Results revealed lower binding energies and higher affinities, of nearly all the phytochemicals with respect to Pentamidine, indicating their leishmanicidal potential. Norcowanin showed the lowest average binding of - 9.8 kcal/mol against all the three enzymes under study.