In silico Exploration of Pharmacological and Molecular Descriptor Properties of Salacinol and Its Related Analogues

Abstract

Salacinol and its related analogues have been known for their potent α-glucosidase inhibitor activity and making them interesting candidates for a new type of anti-diabetic agent. Therefore, it is essential to investigate the physicochemical properties, pharmacological parameters, and toxicity profile of these anti-diabetic agents. In this study, a comprehensive in-silico approach was used to explore the absorption, distribution, metabolism, excretion, and toxicity profiles of salacinol and its related analogues. In addition, to gain a better knowledge of structural and electrical characteristics, global and local reactivity descriptors, and molecular electrostatic potential were calculated and discussed by using DFT at the B3LYP/6–311++G (d, p) level of theory. The results explored that all the studied compounds have low GI absorption and are substrates for P-glycoprotein. None of the compounds can cross the BBB, and none of the compounds are inhibitors of cytochrome P450 isoenzymes. We also found that all compounds have various potential to interact with a wide range of biological targets, including GPCRs, enzymes, ion channels, kinases, and nuclear receptors. Additionally, all compounds have low toxicity and are unlikely to cause any major health hazards in terms of hepatotoxicity, mutagenicity, cardiotoxicity, cytotoxicity, and immunotoxicity. The molecular electrostatic potential map shows that the negative potential sites are in electronegative oxygen atoms, while the positive potential sites are around the hydrogen atoms. The present study concludes that salacinol and its analogues might be a promising safe and effective candidate for the development of therapeutic drugs derived from natural sources. However, some of their properties should be considered in the context of drug development and tissue protection strategies.