Organic Molecular Strategy to Prevent Diabetes: An In Silico Screening of Berberine and Biguanides as Visfatin Antagonists

Diabetes mellitus remains a critical health problem for the world population. Visfatin is a potential target for the effective treatment of type 2 diabetes mellitus (T2DM). Several biguanides, such as Berberine (a natural isoquinoline alkaloid) and Metformin, Phenformin, and Buformin (biguanide-derived antidiabetic drugs), present well-recognized antidiabetic effects. Thus, in this study, using molecular docking, density functional theory (DFT), ADMET, and drug-likeness approaches, the visfatin-inhibiting activity of Berberine and Biguanides for T2DM treatment was investigated. Berberine and Biguanide compounds have favorable pharmacokinetic and physicochemical properties, suggesting that both can be considered safe, orally bioavailable candidates. As lipophilicity, solubility, and Csp3 refinement improve, drugs exhibit better drug-like properties and are more advanced in the drug discovery process. Berberine had a binding free energy of -8.5 kcal/mol. The complex formed 2 hydrogen bonds, including a classical H-bond to Gln92 and Lys189 at an unusually short distance of 2.0 Å, as well as eleven hydrophobic interactions, rendering the compound, compared to Biguanides, the most efficient of all solids bearing potential visfatin.