Exploring natural product library as potential target against sterol C-24 methyltransferase protein of Leishmania donovani
Year: 2024
Type: article
Abstract: Natural product offers an ocean of biologically active compounds that have diverse functionality. Thus, the present study aims for the exploration of natural product molecules for their leishmanicidal potency. Primary evaluation at 50 µM concentration revealed that out of 560 molecules, 38 compounds demonstrated a percentage killing of >50%. Next, the dose-dependent investigation showed that six active hits displayed the IC50 value ranging from 0.47 to 14.2 µM. Further, the molecular docking analysis using the alpha fold structure of Sterol C-24 methyltransferase of Leishmania donovani (LdSMT) (an enzyme absent in mammalian host) unveiled the strong binding affinity with top two hits namely shatavarin IV (−7.9 kcal/mol) and 6-methoxydihydrochelerythrine (−7.6 kcal/mol). Also, in silico studies were supported by the alterations in ergosterol content in the parasites treated with these two potent hits. In conclusion, our study suggests that the two potent hits inhibit the Leishmania parasite growth by hindering sterol biosynthesis.
Source: Natural Product Research
Authors: Diksha Kumari, Harjot Kaur, Tashi Palmo, Amit Nargotra, Kuljit Singh
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4401715343