Abstract
To isolate four phytochemicals (Lapachol, Peshawarquinone- a novel Naphthoquinone, Indanone derivatives and Lapachone), from the methanolic fraction of Heterophragma Adenophyllum Seem, were screened for possible inhibitory potential against urease, a key enzyme involved in gastrointestinal pathologies. To provide additional insights, in Silico docking studies were carried out to study the mechanism of inhibition by using Molecular Operating Environment (MOE). The studied phytochemicals inhibited urease, lapachone (4) inhibition was weak (IC50 = 87.3 + 2.17 mu M), while the peshawarquinone (2) and indanone derivatives (3) significantly inhibited with IC50 = 19.8 + 0.56 and 21.9 + 1.12 mM, respectively. Interestingly, lapachol (1) showed potent activity (IC50 = 23.1 + 0.14 mu M) as compared to the positive control thiourea (IC50 = 21 + 0.23 mu M). In silico docking studies were carried out to study the mechanism of inhibition of Jack-beans urease (JBU) by using Molecular Operating Environment (MOE). Docking results showed that inactivation of the JBU is due to the interaction of compounds with Ni atom and the entrance flap-residues especially with CME592 (a modified cysteine residue). Phytochemicals isolated from H. adenophyllum show promising results to be exploited as a urease inhibitor in managing Helicobacter pylori infection implicated in gastrointestinal diseases. (C) 2021 SAAB. Published by Elsevier B.V. All rights reserved.