β-Sitosterol from Ifloga spicata (Forssk.) Sch. Bip. as potential anti-leishmanial agent against leishmania tropica: Docking and molecular insights

• Published in: Steroids
• Main Author: Majid Shah S.; Ullah F.; Ayaz M.; Sadiq A.; Hussain S.; Ali Shah A.-U.-H.; Adnan Ali Shah S.; wadood A.; Nadhman A.
• Format: Article
• Language: English
• Published: Elsevier Inc. 2019
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85065833307&doi=10.1016%2fj.steroids.2019.05.001&partnerID=40&md5=90f56de011f66d25478360acf7b345b7

The current study was aimed to evaluate the anti-leishmanial potentials of β-sitosterol isolated from Ifloga spicata. The anti-leishmanial potential of β-sitosterol is well documented against Leishmania donovani and Leishmania amazonensis but unexplored against Leishmania tropica. Structure of the compound was elucidated by FT-IR, mass spectrometry and multinuclear (1H and 13C) magnetic resonance spectroscopy. The compound was evaluated for its anti-leishmanial potentials against L. tropica KWH23 using in vitro anti-promastigote, DNA interaction, apoptosis, docking studies against leishmanolysin (GP63) and trypanothione reductase (TR) receptors using MOE 2016 software. β-sitosterol exhibited significant activity against leishmania promastigotes with IC50 values of 9.2 ± 0.06 μg/mL. The standard drug glucantaime showed IC50 of 5.33 ± 0.07 µg/mL. Further mechanistic studies including DNA targeting and apoptosis induction via acridine orange assay exhibited promising anti-leishmanial potentials for β-sitosterol. Molecular docking with leishmanolysin (GP63) and trypanothione reductase (TR) receptors displayed the binding scores of β-sitosterol with targets TR and GP63 were −7.659 and −6.966 respectively. The low binding energies −61.54 (for TR) and −33.24 (for GP63) indicate that it strongly bind to the active sites of target receptors. The results confirmed that β-sitosterol have considerable anti-leishmanial potentials and need further studies as potential natural anti-leishmanial agent against L. tropica. © 2019