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In Silico Analysis of Novel Azetidinone Substituted Benzotriazole and Benzimidazole Derivatives as Plasmodium Falciparum Glutamate Dehydrogenase Inhibitors


Affiliations
1 Research Scholar, Faculty of Pharmacy, RK University, Rajkot, Gujarat, India
2 Department of Pharmaceutical Chemistry, School of Pharmacy, R K University, Rajkot, Gujarat, India
3 Departmet of QA and Chemistry, Saraswati Institute of Pharmaceutical Sciences, Dhanap, Di. Gandhinagar, Gujarat, India
     

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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.

Keywords

Glutamate dehydrogenase, in silico, Chloroquine, Mefloquine, NADP.
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  • In Silico Analysis of Novel Azetidinone Substituted Benzotriazole and Benzimidazole Derivatives as Plasmodium Falciparum Glutamate Dehydrogenase Inhibitors

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Authors

Sandip N. Badeliya
Research Scholar, Faculty of Pharmacy, RK University, Rajkot, Gujarat, India
Pankaj P. Kapupara
Department of Pharmaceutical Chemistry, School of Pharmacy, R K University, Rajkot, Gujarat, India
Ankit B. Chaudhary
Departmet of QA and Chemistry, Saraswati Institute of Pharmaceutical Sciences, Dhanap, Di. Gandhinagar, Gujarat, India

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.

Keywords


Glutamate dehydrogenase, in silico, Chloroquine, Mefloquine, NADP.

References