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Molecular Docking Studies on the Interaction of Four Malagasy Cytotoxic Compounds with Angiogenesis Target Protein HIF-1α and Human Androgen Receptor and Their ADMET properties


Background and objectives: Cancer is a significant public health problem worldwide and constitutes the second leading cause of death after cardiovascular disease. This study was thus designed to identify new natural compounds from Malagasy medicinal plants traditionally used to treat cancer.

Methodology: In silico analyses by molecular docking to model ligand-protein interactions, and by SwissADME and ADMET webservers to establish the pharmacokinetic profile of the four investigated compounds in interaction with the angiogenesis target protein HIF-1α/breast cancer (PDB ID: 3KCX) and human androgen receptor/prostate cancer (PDB ID: 1E3G) were performed.

Results: The docking results show that the HIF-1α receptor has the best binding energy when it interacts with compound 1 (1’,4-dihydroxy-2,3’-dimethyl-1,2’-binapthyl-5,5’,8,8’-tetraone: -8.49 kcal/mol) followed by compound 3 ((E)-5,6-dimethyl-2-(2-methyl-3-(prop-1-enyl)phenyl)-2H-chromene: -8.43 kcal/mol), compound 2 (6’-ethoxy-1’3’-dihydroxy-4,6-dimethyl-1,2’-binaphthyl-2,5’,8,8’-tetraone: -7.80 kcal/mol) and compound 4 (methyl 10-hydroxy-2,4a,6a,9,12b,14a-hexamethyl-11-oxo-1,2,3,4,4a,5,6,6a,11,12b,13,14,14a,14b-tetradecahydropicene-2- carboxylate : -7.63 kcal/mol). The receptor 1E3G displayed poor binding affinity energy to all tested compounds with energy value above -11.99 Kcal/mol (co-crystal). Based on the H-bonding interaction, ligands 1 and 2 displayed good pharmacophore profile to both protein targets 3KCX and 1E3G. The ligand 3 does not interact with the selected receptors via hydrogen bonds. The pharmacokinetic profile of these phyto-compounds revealed that they are orally active and safe. They were isolated and their chemical structures were elucidated previously by our teamusingchromatographic and spectroscopic techniques(LC/MS/NMR).

Conclusion: The ligands 1 and 2 can be considered as hits since they are non-carcinogenic and non-hepatotoxic, and could thus be useful as alternative therapy in breast than in prostate cancer. 


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How to Cite

Ngbolua, K.- te-N. (2023). Molecular Docking Studies on the Interaction of Four Malagasy Cytotoxic Compounds with Angiogenesis Target Protein HIF-1α and Human Androgen Receptor and Their ADMET properties. Discovery Phytomedicine - Journal of Natural Products Research and Ethnopharmacology, 8(3).




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