Two new aggreceride derivatives and other chemical constituents from the stems of Tarenna conferta Benth and their potential antileishmanial activity against Leishmania donovani promastigotes: Insight from molecular docking analysis

Tarenna conferta Benth is traditionally used to treat fever, headaches, parasitic and skin diseases. The aim of this study was to identify potential antileishmanial bioactive compounds from T. conferta and in silico studies against target receptors (2JK6 and 2W0H). The performance of successive chromatographic techniques followed by characterization using NMR (1D and 2D) as well as HR-ESIMS analyses, of methylene choride fraction of the stems of T. conferta, led to the identification of two unprecedented derivatives i.e. a new derivative of a dicarboxylic acid (1) and a new hydroxy ester derivative (2), with seven known compounds 3, 4, 5, 6, 7, 8 and 9. Compounds 1, 3 and 4 displayed highly potent antileishmanial activity against Leishmania donovani promastigotes with IC₅₀ values of 3.586 ± 0.554 μg/mL, 0.154 ± 0.8123 μg/mL and 0.789 ± 0.105 μg/mL respectively, compared to amphotericine B (IC₅₀ = 0.198 ± 0.704 μM), used as positive control. However crude extract exhibited significant antileishmanial activity against L. donovani (MHOM/SD/62/1S) promastigotes (IC₅₀ 56.860 ± 1.755 μg/mL) and showed no cytotoxicity on RAW 264.7 macrophage cells. The molecular docking provides a captivating glimpse into the intricate interactions between compounds 1, 2, 3, and 4 and the target receptors (2JK6 and 2W0H). The results revealed that, compounds 1, 3, and 4 consistently displayed strong binding affinities and hydrogen bond interactions, showcasing their potential for effective therapeutic interventions. Compounds 2 and 3 exhibit moderate binding affinities with essential amino acids. In terms of potential drug development, compound 4 emerges as a standout candidate due to its exceptionally high binding affinities and specific interactions.