Laboratory of Pharmaceutical and Medicinal Chemistry (PharMedChem), Federal University of Amapá, Rod. JK, Km 02, Macapá, Brazil.
Computational Laboratory of Pharmaceutical Chemistry, Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
J Mol Model. 2022 Aug 17;28(9):258. 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 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.
寻找肥胖症的新的药理学替代物的基础是设计和开发能够帮助减肥的化合物，以便它们可以安全有效地长期使用，同时保持其功能。内源性大麻素系统通过增加食欲信号和减少饱腹感信号与肥胖有关。大麻是一种具有多药效潜力的药用植物，已被广泛研究用于各种药用目的。出于对肥胖症的治疗目的，对其天然大麻素（也称为植物大麻素）进行计算机评估源自已呈现出这一结果的合成大麻素化合物的存在，但这些化合物不能保证患者的安全。为了从大麻植物大麻素中找到具有与药理学靶标大麻素受体 1 相互作用潜力的新分子，进行了基于药效团的虚拟筛选，包括评估物理化学、药代动力学、毒理学预测和分子对接。从 ZINC 数据库获得的结果表明，Zinc 69（ZINC33053402）和 Zinc 70（ZINC19084698）分子具有成为有前途的抗肥胖药物的潜力。通过分析均方根偏差（RMSD）值，分子动力学（MD）研究表明，这两种复合物都是稳定的，而结合自由能值表明所选结构可以相互作用并抑制其催化活性。
