Pharmacophore-based virtual screening from phytocannabinoids as antagonist r-CB1

• Published in: Journal of molecular modeling 2022-09, Vol.28 (9), p.258-258, Article 258
• Main Authors: Correia, Lenir C., Ferreira, Jaderson V., de Lima, Henrique B., Silva, Guilherme M., da Silva, Carlos H. T. P., de Molfetta, Fábio A., Hage-Melim, Lorane I. S.
• Format: Article
• Language: English
• Subjects: Cannabis; Catalytic activity; Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Computer Appl. in Life Sciences; Computer Applications in Chemistry; Energy value; Free energy; Herbal medicine; Molecular docking; Molecular dynamics; Molecular Medicine; Obesity; Original Paper; Pharmacology; Screening; Theoretical and Computational Chemistry; Weight control; Weight loss; Zinc
• ISSN: 1610-2940; 0948-5023
• DOI: 10.1007/s00894-022-05219-3

Search for new pharmacological alternatives for obesity is based on the design and development of compounds that can aid in weight loss so that they can be used safely and effectively over a long period while maintaining their function. The endocannabinoid system is related to obesity by increasing orexigenic signals and reducing satiety signals. Cannabis sativa is a medicinal plant of polypharmaceutical potential that has been widely studied for various medicinal purposes. The in silico evaluation of their natural cannabinoids (also called phytocannabinoids) for anti-obesity purpose stems from the existence of synthetic cannabinoid compounds that have already presented this result, but which did not guarantee patient safety. In order to find new molecules from C. sativa phytocannabinoids, with the potential to interact peripherally with the pharmacological target cannabinoid receptor 1, a pharmacophore-based virtual screening was performed, including the evaluation of physicochemical, pharmacokinetic, toxicological predictions and molecular docking. The results obtained from the ZINC 12 database pointed to Zinc 69 (ZINC33053402) and Zinc 70 (ZINC19084698) molecules as promising anti-obesity agents. Molecular dynamics (MD) studies disclose that both complexes were stable by analyzing the RMSD (root mean square deviation) values, and the binding free energy values demonstrate that the selected structures can interact and inhibit their catalytic activity.