Synthesis, activity and in silico studies of novel bisindolylmethanes from xylochemical 5-hydroxymethylfurfural as antidiabetic agents

Abstract

A novel series of 3,3'-bisindolylmethanes was successfully synthesized from a xylochemical 5-hydroxymethylfurfural, by condensing with indoles 3a-l employing a green mechanochemical method using silica-sulphamic acid as grinding material in excellent yield. The synthesized molecules 5a-i were evaluated for their pharmacological activity. The antioxidant properties were explored by examining the radical scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and the antidiabetic activities were studied by the Alpha-amylase and Alpha-glucosidase assay and compared with acarbose. All the synthesized compounds showed comparable Alpha-amylase inhibitory activity and better Alpha-glucosidase inhibitory activity than that of acarbose. Among the synthesized compounds 5f showed 5-fold Alpha-glucosidase inhibition to that of acarbose. All synthesized compounds were also evaluated by docking studies for binding with Alpha-amylase and Alpha-glucosidase enzyme and drug-likeness studies. Compounds 5c and 5f were seen to bound with a minimum energy of -9.48 kcal/mol and -9.20 kcal/mol with Alpha-amylase enzyme and -9.11 kcal/mol and -9.00 kcal/mol with Alpha-glucosidase enzyme.