Therapeutic Potential and Molecular Docking Perspective of Six Medicinal Plants against the Human SIRT-6 Protein Implicated in Type-2 Diabetes.

Abstract

Despite the vast array of approved anti-diabetic drugs and the fact that these medications are often associated with other serious side effects like cardiovascular disease, weight gain, liver disorders, and countless others, the prevalence of Type-2 diabetes is soaring. Through in silico analysis, our study seeks to elucidate the anti-diabetic potential of six (6) medicinal plants Buchholzia coriacea, Vernonia amygdalina, Mimosa pudica, Momordica charantia, Bergenia ciliate, and Mangifera indica. Methods: Twenty-nine (29) bioactive compounds were selected from the six plants. Metformin and Miglitol are used as the control drug in this study. PubChem, an online server, was used to get the 3D structure of the bioactive compounds and the control drugs. The protein data bank was used to retrieve the crystal structure of the SIRT6 protein. The SwissADME online server was used for the Drug-likeness of the bioactive compounds and the control drugs. AutoDock was used for the molecular docking of compounds that passed the drug-likeness with the SIRT6 active site. The protein-ligand complexes were analyzed using a protein-ligand interaction profiler and proteins plus web server. The Molinspiration online server was used to predict compound bioactivity. The ADMETlab webserver was used to determine the ligands' ADMET properties. Results: The drug-likeness screening of the twenty-nine compounds and the control drugs revealed that twenty-five compounds have zero or one violation of Lipinski's rule of five. Metformin and Miglitol have zero violations. The docking analysis revealed that twenty out of the twenty-five compounds docked against the protein target have better binding affinity than the control drugs. Catechin, Luteolin, Chlorogenic acid, and Mimopudine have an excellent binding affinity of -8.4 kcal/mol -7.8 kcal/mol, -7.7 kcal/mol, and -7.5 kcal/mol, respectively. In contrast, Metformin and Miglitol have binding scores of -4.8 and -5.1 kcal/mol, respectively. Conclusions: Therefore, the greater binding affinity of the twenty compounds compared to the control drugs suggests that these compounds possess anti-diabetic properties with good interaction with the SIRT6 protein. However, this research needs further validation with molecular dynamics studies and in-vitro and in-vivo evaluation.