The hypoglycemic potential of genus Morus: Bioavailability and molecular docking between secondary metabolites of Morus alba L. and sulfonylurea receptor 1 (SUR1)

Resumen

It is reported the bioavailability analysis for ten secondary metabolites with hypoglycemic activity from Morus alba L. Additionally, the molecular similarity analysis of each metabolite is presented and compared with nateglinide, nepaglinide, and other hypoglycemic molecules referents. The mode of interaction through molecular docking between each secondary metabolite and the zone of action for repaglinide (RPG) in the sulphonylurea receptor 1 (SUR1) is also presented. The molecular geometry for structures was optimized with HF/6-31+G (d,p) level and functional density methods at the CAM-B3LYP/6-31+G (d,p) level. The bioavailability and molecular docking calculations were performed using the algorithms incorporated in the chemo informatic servers and AutoDock Vina. The results show that the structures studied lead a good permeability through the cell membrane, by complying with Lipinski's "rule of 5"; namely: log P<5, molecular weight <500, acceptor sites for hydrogen bonds <10, donor sites for hydrogen bonds <5 and a molecular volume <500. The molecular similarity was evaluated by averaging geometric parameters (3D-Shape) and electrostatic potential (ESP). The results show that most secondary metabolites would have a similar mode of action as the neteglinide, with the average similarity between 0.72 and 0.80. This last idea is reinforced by the results for molecular docking with the nepaglinide active site of SUR1, highlighting the interaction of the molecules studied with the amino acid residues: Arg-1246, Tyr-377, Asn-437, Leu-434, Phe-433, Trp-430, and Ile-381, with arranging interaction-free energy between -5.2 and -7.9 Kcal/mol.