Department of Biochemistry, Genetics and Microbiology, University of Pretoria, Pretoria, Hillcrest 0083, South Africa.
Structural Bioinformatics and High Performance Computing Research Group (BIO-HPC), Universidad Católica de Murcia 30107, Spain.
Molecules. 2019 May 24;24(10):2002. doi: 10.3390/molecules24102002.
Medicinal plants containing complex mixtures of several compounds with various potential beneficial biological effects are attractive treatment interventions for a complex multi-faceted disease like diabetes. In this study, compounds identified from African medicinal plants were evaluated for their potential anti-diabetic activity. A total of 867 compounds identified from over 300 medicinal plants were screened with the DIA-DB web server (http://bio-hpc.eu/software/dia-db/) against 17 known anti-diabetic drug targets. Four hundred and thirty compounds were identified as potential inhibitors, with 184 plants being identified as the sources of these compounds. The plants and were identified as new sources rich in compounds with a potential anti-diabetic activity. The major targets identified for the natural compounds were aldose reductase, hydroxysteroid 11-beta dehydrogenase 1, dipeptidyl peptidase 4, and peroxisome proliferator-activated receptor delta. More than 30% of the compounds had five or more potential targets. A hierarchical clustering analysis coupled with a maximum common substructure analysis revealed the importance of the flavonoid backbone for predicting potential activity against aldose reductase and hydroxysteroid 11-beta dehydrogenase 1. Filtering with physiochemical and the absorption, distribution, metabolism, excretion and toxicity (ADMET) descriptors identified 28 compounds with favorable ADMET properties. The six compounds-crotofoline A, erythraline, henningsiine, nauclefidine, vinburnine, and voaphylline-were identified as novel potential multi-targeted anti-diabetic compounds, with favorable ADMET properties for further drug development.
含有多种化合物的复杂混合物的药用植物具有各种潜在的有益生物学效应，对于糖尿病等复杂的多方面疾病来说，是一种有吸引力的治疗干预手段。在这项研究中，从非洲药用植物中鉴定出的化合物被评估其潜在的抗糖尿病活性。在 DIA-DB 网络服务器（http://bio-hpc.eu/software/dia-db/）上，使用 17 种已知的抗糖尿病药物靶点，对来自 300 多种药用植物的 867 种化合物进行了筛选。鉴定出 430 种化合物为潜在抑制剂，其中 184 种植物被鉴定为这些化合物的来源。和被鉴定为富含具有潜在抗糖尿病活性的化合物的新来源。天然化合物的主要靶点是醛糖还原酶、羟甾体 11-β 脱氢酶 1、二肽基肽酶 4 和过氧化物酶体增殖物激活受体 δ。超过 30%的化合物有五个或更多的潜在靶点。层次聚类分析结合最大公共子结构分析表明，黄酮骨架对于预测对醛糖还原酶和羟甾体 11-β 脱氢酶 1的潜在活性具有重要意义。使用物理化学和吸收、分布、代谢、排泄和毒性（ADMET）描述符进行过滤，鉴定出 28 种具有良好 ADMET 特性的化合物。六种化合物——克罗托福林 A、赤醇、henningsiine、nauclefidine、vinburnine 和 voaphylline——被鉴定为新型潜在的多靶点抗糖尿病化合物，具有良好的 ADMET 特性，适合进一步药物开发。
