Abstract

Aliyu Hamidu Ahmed* and Yusuf Ibrahim Alkali

ABSTRACT

The use of computer-aided methods in drug discovery, prediction of toxicity and pharmacokinetic profile is an area of research with increasing interest. This study was carried out in order to determine the pharmacokinetic profile, toxicity and potential to inhibit the SGT2 of Bacosine, bergenin, tiliroside and Swertiamarin using in silico tools. SwissADME server was used to determine their Blood brain barrier (BBB) permeation, Human Intestinal Absorption (HIA), P-glycoprotein substrate (P-gp), cytochrome P450 isoform inhibition, Skin permeation Log Kp and bioavailability score. Protox-II server was used to predict the organ toxicities and toxicological end points of the ligands and their LD50. AutoDock Vina was used for the docking studies. Bacosine and bergenin showed high human intestinal absorption (HIA) while Swertiamarin and tiliroside showed low HIA. All the compounds do not permeate the blood brain barrier (BBB). The compounds in this study are not substrates of permeability glycoprotein (P-gp). All the compounds in this study do not inhibit any of the CYP450 enzymes except Bacosine which inhibits CYP2C9. The compounds do not permeate the skin. Tiliroside and bergenin show immunotoxicity while Bacosine was active for carcinogenicity. Bacosine and tiliroside have lower binding energy (-9.1 kcal/mol and -11.0 kcal/mol respectively) than the standard drug Dapagliflozin. According to the findings of this study, Bacosine was found to have good pharmacokinetic profile, low toxicity and binding affinity higher than the standard drug. Bacosine may serve as a lead compound in discovery of new antidiabetic agents.