In silico Study of Coumarins Derivatives With Potential Use in Systemic Diseases

Abstract

Coumarins have been widely used in various human systemic diseases; however, their molecular action is not known in many cases. In silico studies are an option to explore the interaction of molecules with molecular targets and to obtain explanations for these biological activities. SwissTargetPrediction is an accepted tool to obtain potential biological targets for coumarin derivatives. Some carbonic anhydrases (CAs), enzymes related to the central nervous system (CNS), and estrogen receptors (ER) were evaluated vis à vis coumarins holding an electron donor (EDG) or an electron-withdrawing group (EWG). Molecular docking studies using Schrödinger carried out with some selected proteins showed that EDG and produces the best binding coupling energy (BCE) in CAs and ER. Substituents in the aromatic ring increased the BCE in targets related to CNS enzymes; EDG and EWG at positions 3 or 4 in coumarins had better activity in CAs. Also, in CAs, coumarins derivatives presented better BCE than commercial inhibitors. In ER, no competitive activity to estradiol was obtained from coumarins. All In silico results demonstrated the selective influence of the type of substitution and their position on the BCE that could permit better coumarin derivatives in protein targets implicated in human systemic diseases.