Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga, Punjab, India.
Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, Taif, Saudi Arabia.
J Biomol Struct Dyn. 2023;41(21):12171-12185. doi: 10.1080/07391102.2023.2166122. Epub 2023 Jan 17.
Monoamine oxidases (MAOs) are flavo-enzymes that aid in the oxidative deamination of neurotransmitters like dopamine, serotonin, and epinephrine. MAO inhibitors are antidepressants that work by preventing the breakdown of brain neurotransmitters and regulating mood. MAO inhibitors that use the chromone (1-benzopyran-4-one) structure have been found to be quite effective in studies. The current study involves the creation of pharmacophore models, 3-D QSAR, virtual screening, and docking investigations, all of which are evaluated using various criteria. The investigation included 39 ligands that emerged pharmacophore AHRRR_1, as the best pharmacophore model with a survival score of 5.6485. The 3D QSAR investigation revealed a significant model with the values of = 0.9064 and = 0.8239. Docking study revealed that compound 18 had the highest docking (-10.402 kcal/mol) score in the series and showed interactions with the essential amino acid TYR398 required for MAO inhibitory activity. ZINC compounds were screened using the created pharmacophore model, which was followed up with a virtual screening study. The ZINC compounds with the best XP docking scores are ZINC03113255, ZINC07777127, ZINC05166353 and ZINC09341502 (with docking scores -10.021, -9.486, -8.031 and -7.792 kcal/mol, respectively). ZINC03113255, which showed the best score, has binding interactions with amino acid residues, TYR326, TYR398 and LYS296 of monoamine oxidase B. The ADME analysis demonstrated the compound's drug-like characteristics. The findings of this study may be used in the development of chromone compounds that target the MAO inhibitor.Communicated by Ramaswamy H. Sarma.
单胺氧化酶（MAO）是一种黄素酶，有助于多巴胺、血清素和肾上腺素等神经递质的氧化脱氨。MAO 抑制剂是通过阻止大脑神经递质分解和调节情绪来起作用的抗抑郁药。使用色酮（1-苯并吡喃-4-酮）结构的 MAO 抑制剂在研究中被发现非常有效。本研究涉及创建药效团模型、3-D QSAR、虚拟筛选和对接研究，所有这些都使用各种标准进行评估。研究包括 39 个配体，它们产生了药效团 AHRRR_1，作为最好的药效团模型，存活分数为 5.6485。3D QSAR 研究揭示了一个具有显著模型的 = 0.9064 和 = 0.8239 值。对接研究表明，在该系列化合物中，化合物 18 的对接（-10.402kcal/mol）得分最高，并与 MAO 抑制活性所需的必需氨基酸 TYR398 相互作用。使用创建的药效团模型对 ZINC 化合物进行筛选，随后进行虚拟筛选研究。ZINC 化合物的最佳 XP 对接分数是 ZINC03113255、ZINC07777127、ZINC05166353 和 ZINC09341502（对接分数分别为-10.021、-9.486、-8.031 和-7.792kcal/mol）。ZINC03113255 显示出最好的分数，与单胺氧化酶 B 的氨基酸残基 TYR326、TYR398 和 LYS296 具有结合相互作用。ADME 分析表明该化合物具有类药性特征。本研究的结果可用于开发针对 MAO 抑制剂的色酮化合物。由 Ramaswamy H. Sarma 传达。
