Exploring African Medicinal Plants for Potential Anti-Diabetic Compounds with the DIA-DB Inverse Virtual Screening Web Server

• Main Authors: Andreia S.P. Pereira, Helena den Haan, Jorge Peña-García, Marién M. Moreno, Horacio Pérez-Sánchez, Zeno Apostolides
• Format: Article
• Language: English
• Published: MDPI AG 2019-05-01
• Series: Molecules
• Subjects: diabetes; anti-diabetic; DIA-DB; medicinal plants; <i>in silico</i>; virtual screening
• Online Access: https://www.mdpi.com/1420-3049/24/10/2002

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 <i>in silico</i> 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 <i>Argemone ochroleuca</i>, <i>Clivia miniata</i>, <i>Crinum bulbispermum</i>, <i>Danais fragans</i>, <i>Dioscorea dregeana</i>, <i>Dodonaea angustifolia</i>, <i>Eucomis autumnalis</i>, <i>Gnidia kraussiana</i>, <i>Melianthus comosus</i>, <i>Mondia whitei</i>, <i>Pelargonium sidoides</i>, <i>Typha capensis</i>, <i>Vinca minor</i>, <i>Voacanga africana</i>, and <i>Xysmalobium undulatum</i> 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&#8212;crotofoline A, erythraline, henningsiine, nauclefidine, vinburnine, and voaphylline&#8212;were identified as novel potential multi-targeted anti-diabetic compounds, with favorable ADMET properties for further drug development.