Article: Identification of potential anti-obesity drug scaffolds using molecular modelling Journal: International Journal of Computational Biology and Drug Design (IJCBDD) 2021 Vol.14 No.2 pp.103 - 129 Abstract: The prevalence of obesity has remarkably increased in recent decades. An important strategy to combat obesity is to reduce the imbalance between energy intake and expenditure. Pancreatic lipase (PL) and acetyl coenzyme A carboxylase 2 (ACC2) are two promising targets for the therapeutic treatment of obesity. In silico techniques including high throughput virtual screening, binding free energy calculations, and molecular dynamics (MD) simulation were used to identify molecules with good potential to inhibit these targets. Derivatives of coumaran-3-one and dioxabicyclo[3.3.0]octane-2,6-diamine are likely to possess inhibitory potential against PL while acetamide and hexanamide derivatives showed inhibitory potential against ACC2. MD simulations of the top scoring molecules confirmed that the identified molecules bind strongly and consistently in the binding site of PL and ACC2. The shortlisted molecules exhibited better interactions and affinity when compared to control molecules and thus could be explored as scaffolds for the development of anti-obesity drugs. Inderscience Publishers - linking academia, business and industry through research

Title: Identification of potential anti-obesity drug scaffolds using molecular modelling

Authors: Amie Jobe; Bincy Baby; Amanat Ali; Ranjit Vijayan

Addresses: Department of Biology, College of Science, United Arab Emirates University, P.O. Box 15551, Al Ain, UAE ' Department of Biology, College of Science, United Arab Emirates University, P.O. Box 15551, Al Ain, UAE ' Department of Biology, College of Science, United Arab Emirates University, P.O. Box 15551, Al Ain, UAE ' Department of Biology, College of Science, United Arab Emirates University, P.O. Box 15551, Al Ain, UAE

Abstract: The prevalence of obesity has remarkably increased in recent decades. An important strategy to combat obesity is to reduce the imbalance between energy intake and expenditure. Pancreatic lipase (PL) and acetyl coenzyme A carboxylase 2 (ACC2) are two promising targets for the therapeutic treatment of obesity. In silico techniques including high throughput virtual screening, binding free energy calculations, and molecular dynamics (MD) simulation were used to identify molecules with good potential to inhibit these targets. Derivatives of coumaran-3-one and dioxabicyclo[3.3.0]octane-2,6-diamine are likely to possess inhibitory potential against PL while acetamide and hexanamide derivatives showed inhibitory potential against ACC2. MD simulations of the top scoring molecules confirmed that the identified molecules bind strongly and consistently in the binding site of PL and ACC2. The shortlisted molecules exhibited better interactions and affinity when compared to control molecules and thus could be explored as scaffolds for the development of anti-obesity drugs.

Keywords: obesity; pancreatic lipase; acetyl coenzyme A carboxylase 2; molecular dynamics; molecular docking; high throughput virtual screening; anti-obesity drug scaffolds; anti-obesity drug discovery.

DOI: 10.1504/IJCBDD.2021.115674

International Journal of Computational Biology and Drug Design, 2021 Vol.14 No.2, pp.103 - 129

Received: 18 Jun 2020
Accepted: 23 Sep 2020
Published online: 16 Jun 2021 *

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Title: Identification of potential anti-obesity drug scaffolds using molecular modelling

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