loading page

EXPLORING THE ACTIVITY OF SINIGRIN, A GLUCOSINOLATE AS AN ANTIMALARIAL
  • +2
  • Neha Walter,
  • Varun Gorki,
  • Monika Chauhan,
  • Neelima Dhingra,
  • Sukhbir Kaur
Neha Walter
Panjab University Faculty of Science
Author Profile
Varun Gorki
Panjab University Faculty of Science
Author Profile
Monika Chauhan
Panjab University
Author Profile
Neelima Dhingra
Panjab University
Author Profile
Sukhbir Kaur
Panjab University Faculty of Science

Corresponding Author:[email protected]

Author Profile

Abstract

Background and Purpose: Plant derived antimalarials are indispensable for malaria treatment and a reliable source of new drugs. The present study first time explores antimalarial efficacy of sinigrin present in ethanolic whole plant extract of Thlaspi arvense (EWETA) using in vitro, in silico and in vivo strategies. Experimental Approach: From EWETA, sinigrin was revalidated and quantified using HPLC. Schizont maturation inhibition assay was used to assess its in vitro antiplasmodial activity followed by the determination of cytotoxicity. Further, docking study was performed on key metabolic enzymes of P. falciparum using V-Life MDS tool. Peter’s 4-day test was employed to assess in vivo suppressive activity. Key Results: Sinigrin exhibited promising activity against both chloroquine (CQ)-resistant (RKL-9) IC50 5.14 μg/mL and CQ-sensitive (3D7) IC50 5. 47 μg/mL strains of P. falciparum and was safe in both in vitro (CC50> 640 μg/mL) and in vivo (LD50 > 2 g/kg) toxicity studies. In addition, virtual screening showed hydrogen bonding, hydrophobic and van der Waals interactions with amino acid residues of 3BPM (falcipain-3). Sinigrin illustrated good (ED50< 50 mg/kg) suppressive activity against P. berghei in monotherapy and enhanced the activity of artesunate (50 mg/kg) in combination with 100% survival and no parasite recrudescence. These observations are further corresponded and supported by Differential Leucocyte Count (DLC), biochemical and histopathological studies. Conclusions and implications: The outcomes of in vitro, in silico and in vivo studies suggest sinigrin as a HIT molecule which may potentially be used in many ways in drug and vaccine development approaches.