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

Abstract

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 in silico 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 Argemone ochroleuca, Clivia miniata, Crinum bulbispermum, Danais fragans, Dioscorea dregeana, Dodonaea angustifolia, Eucomis autumnalis, Gnidia kraussiana, Melianthus comosus, Mondia whitei, Pelargonium sidoides, Typha capensis, Vinca minor, Voacanga africana, and Xysmalobium undulatum 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.

A High-Content Screen for the Identification of Plant Extracts with Insulin Secretion-Modulating Activity

“…A. arvensis , S. mukorossi and G. sinensis also showed a significant decrease in cell viability when used at a concentration of 10 µg/mL (see Figure A2 and Figure A3 ). A. arvensis , which was identified as a potential rich source of compounds with antidiabetic activity [ 35 ], led to an increase in insulin secretion when applied at a concentration of 5 µg/mL. P. nigra and A. sativum demonstrated minor effects at all chosen concentrations, but similar to A. julibrissin and L. barbarum , they did not show a significant decrease in cell viability.…”

Assessment of antidiabetic potential and phytochemical profiling of Rhazya stricta root extracts

“…)- P Vincaminol (201188) 24.360 Akuammilan-17-oic acid, methyl ester P P P P P P Strictamine (5324377) 24.647 2H-3,7-Methanoazacycloundecino[5,4-b]indole-9-carboxylic acid, 5-ethyl-1,4,5,6,7,8,9,10-octahydro-, methyl ester, [5S-(5R*,7R*,9S*)]- Cleavamine (425980) 24.761 Phthalic acid, 2-ethylbutyl nonyl ester P 25.092 Vinburnine P P P P P P Eburnamonine (71203) Antidiabetic [ 44 ] 25.817 Phthalic acid, bis(7-methyloctyl) ester P P 26.081 Squalene P P P P P P Antidiabetic [ 45 ] Antioxidant [ 46 ] 26.328 Eburnamenine-14-carboxylic acid, 14,15-dihydro-14-hydroxy-, methyl ester, (3.alpha.,14.alpha.,16.alpha. )- P Vincamine (15376) Antidiabetic Activity [ 44 ] 26.766 Apovincamine P P …”

“…19.526 9-Octadecenoic acid (Z)-, methyl ester P P P P P P P P Antioxidant [42] 19.630 Hexadecane P 25.817 Phthalic acid, bis(7-methyloctyl) ester P P 26.081 Squalene P P P P P P Antidiabetic [45] Antioxidant [46] 26.328 Eburnamenine-14-carboxylic acid, 14,15-dihydro-14hydroxy-, methyl ester, (3.alpha.,14.alpha.,16.alpha. )-P Vincamine (15376) Antidiabetic Activity [44] 26.766 Apovincamine P P P…”

“…After the initial screening, we have found a variety of the compounds of different phytochemical classes through GCMS. Interestingly, among the identified compounds in the SCL fraction, five have already been documented as antihyperglycemic compounds namely; Hexadecane [ 40 ], n-Hexadecanoic acid [ 41 ], Vinburnine, Vincamine [ 44 ] and Squalene [ 45 ]. Some other classes of compounds have also been identified and derivatives of which are reported of antidiabetic potential like Benzofuran [ 51 ], Quinoxaline [ 52 ] Quinoline [ 53 , 54 ], Pyridine [ 55 ], Sydnones [ 56 ] Thioureas [ 57 ] and Isoquinolines [ 58 ].…”

Amino-3,5-Dicyanopyridines Targeting the Adenosine Receptors. Ranging from Pan Ligands to Combined A1/A2B Partial Agonists

“…Nevertheless, while some bioavailability and toxicity parameters fall in the safety range, others indicate some points of concerns for compound 3. In interpreting the contrasting results, it is important to consider that in silico evaluation of the ADMET parameters for a group of approved antidiabetic drugs [41] evidenced not only violation of some of the RO5 (25%) but also the toxicity parameters as the major failures (2-33%).…”