Type 2 diabetes mellitus is one of the most common diseases of the 21st century, caused by a sedentary lifestyle, poor diet, high blood pressure, family history, and obesity. To date, there are no known complete cures for type 2 diabetes. To identify bioactive natural products (NPs) to manage type 2 diabetes, the NPs from the ZINC15 database (ZINC-NPs DB) were screened using a 3D shape similarity search, molecular docking approaches, and ADMETox approaches. Frequently, in silico studies result in asymmetric structures as “hit” molecules. Therefore, the asymmetrical FDA-approved diabetes drugs linagliptin (8-[(3R)-3-aminopiperidin-1-yl]-7-but-2-ynyl-3-methyl-1-[(4-methylquinazolin-2-yl)methyl]purine-2,6-dione), sitagliptin ((3R)-3-amino-1-[3-(trifluoromethyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one), and alogliptin (2-[[6-[(3R)-3-aminopiperidin-1-yl]-3-methyl-2,4-dioxopyrimidin-1-yl]methyl]benzonitrile) were used as queries to virtually screen the ZINC-NPs DB and detect novel potential dipeptidyl peptidase-4 (DPP-4) inhibitors. The most promising NPs, characterized by the best sets of similarity and ADMETox features, were used during the molecular docking stage. The results highlight that 11 asymmetrical NPs out of 224,205 NPs are potential DPP-4 candidates from natural sources and deserve consideration for further in vitro/in vivo tests.

中文翻译：

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作为 DPP-4 抑制剂的天然化合物：3D 相似性搜索、ADME 毒性和分子对接方法

2型糖尿病是21世纪最常见的疾病之一，由久坐的生活方式、不良饮食、高血压、家族史和肥胖引起。迄今为止，没有已知的完全治愈 2 型糖尿病的方法。为了鉴定用于管理 2 型糖尿病的生物活性天然产物 (NPs)，使用 3D 形状相似性搜索、分子对接方法和 ADMETox 方法对来自 ZINC15 数据库 (ZINC-NPs DB) 的 NPs 进行了筛选。通常，计算机研究导致不对称结构作为“命中”分子。因此，FDA 批准的不对称糖尿病药物 linagliptin (8-[(3R)-3-aminopiperidin-1-yl]-7-but-2-ynyl-3-methyl-1-[(4-methylquinazolin-2-yl) )甲基]purine-2,6-dione), 西格列汀 ((3R)-3-amino-1-[3-(trifluoromethyl)-6,8-dihydro-5H-[1,2,4]triazolo[4, 3-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one), 和阿格列汀（2-[[6-[(3R)-3-aminopiperidin-1-yl]-3-methyl-2,4-dioxopyrimidin-1-yl]methyl]benzonitron) 被用作虚拟筛选 ZINC 的查询-NPs DB 并检测新的潜在二肽基肽酶 4 (DPP-4) 抑制剂。在分子对接阶段使用了最有希望的 NP，其特征在于最佳的相似性和 ADMETox 特征集。结果强调，224,205 个 NP 中有 11 个不对称 NP 是来自天然来源的潜在 DPP-4 候选物，值得考虑进一步的体外/体内测试。在分子对接阶段使用了具有最佳相似性和 ADMETox 特征集的特征。结果强调，224,205 个 NP 中有 11 个不对称 NP 是来自天然来源的潜在 DPP-4 候选物，值得考虑进一步的体外/体内测试。在分子对接阶段使用了具有最佳相似性和 ADMETox 特征集的特征。结果强调，224,205 个 NP 中有 11 个不对称 NP 是来自天然来源的潜在 DPP-4 候选物，值得考虑进一步的体外/体内测试。