Coumarin derivatives against diabetics: a systematic target-specific drug repurposing approach via molecular docking-dynamic simulation

Abstract

Coumarin derivatives (CDs) possess diverse pharmacological properties, but their antidiabetic potential is not fully explored. In this perspective, we selected 108 plant-derived CDs and investigated their antidiabetic potency, taking a panel of putative targets: AKT1, ACACB, CDK4, α-amylase, GLUT1, and PTP1B in a computer-aided drug design (CADD) platform. In addition, predicted toxicity, pharmacokinetics, bioavailability, and drug ability profiles of CDs. Further, molecular dynamics (MD) simulations were employed to observe the dynamic behaviour of the two potential CDs (sanandajin or SANA, sinkianone or SINK) and standards (glimepiride or G and resveratrol or RESV) with AKT1 at 100 nanoseconds. Overall, findings reveal that SANA and SINK exhibited stronger binding affinities with AKT1 than standards with lesser toxicity and favorable drug-ability profiles to use as bioactive therapeutic agents for the management of diabetics. The systematic CADD analyses are able to locate potential CDs and encourage further experimental studies for mainstream applications.

Keywords

• Diabetes mellitus
• natural remedy for diabetic
• coumarin derivatives
• molecular docking and MD simulation
• toxicity and drug-ability profiles
• frontiers orbital analysis