In silico analysis of novel azetidinone substituted benzotriazole and benzimidazole derivatives as Plasmodium falciparum glutamate dehydrogenase inhibitors Badeliya Sandip N.1,*, Kapupara Pankaj P.2,**, Chaudhary Ankit B.3,*** 1Research Scholar, Faculty of Pharmacy, RK University, Rajkot, Gujarat, India 2Department of Pharmaceutical Chemistry, School of Pharmacy, R K University, Rajkot, Gujarat, India 3Departmet of QA and Chemistry, Saraswati Institute of Pharmaceutical Sciences, Dhanap, Di. Gandhinagar, Gujarat, India *Corresponding Author E-mail: snb.success@gmail.com
**pankaj.kapupara@rku.ac.in
***ankitbchaudhary@gmail.com
Online Published on 08 June, 2022. Abstract NADP-dependent enzyme Glutamate dehydrogenase is responsible for the maintenance of reduced state in plasmodia. Chloroquine and Mefloquine inhibit glutamate dehydrogenase enzyme and also glutathione reductase like antioxidative enzyme and thioredoxin, inducing oxidative stress. Plasmodia can't survive in the highly oxidized medium. From a detailed study on the SAR of quinolines, a series of compounds were designed and developed using molecular docking, In silico analysis was done using SWISSADME online tool, and bioactivity prediction was performed using Molinspiration online tool. Among the all designed compounds, in the benzotriazole series, compound code 1(d) (−103.22kcal/mol), 1(e) (−102.05kcal/mol), and 1(b) (−100.78 kcal/mol) show good binding affinity. Whereas, in the benzimidazole series, compound code 2(f) (−104.98 kcal/mol), 2(b) (−104.86kcal/mol) and 2(g) (−104.08kcal/mol) shows good binding affinity. The performed research reveals that benzimidazole derivatives offer an advantage over benzotriazole moiety for binding affinity with the enzyme Plasmodium Falciparum glutamate dehydrogenase. Top Keywords Glutamate dehydrogenase, In silico, Chloroquine, Mefloquine, NADP. Top |