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

Steroids. 2019 Aug:148:56-62. doi: 10.1016/j.steroids.2019.05.001. Epub 2019 May 11.

Abstract

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.

Keywords: Apoptosis; DNA interaction; Docking; Leishmania tropica; β-Sitosterol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiprotozoal Agents / chemistry
  • Antiprotozoal Agents / isolation & purification
  • Antiprotozoal Agents / pharmacology*
  • Asteraceae / chemistry*
  • Dose-Response Relationship, Drug
  • Leishmania tropica / drug effects*
  • Molecular Conformation
  • Molecular Docking Simulation*
  • Parasitic Sensitivity Tests
  • Sitosterols / chemistry
  • Sitosterols / isolation & purification
  • Sitosterols / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antiprotozoal Agents
  • Sitosterols
  • gamma-sitosterol