Synthesis, characterization and molecular docking studies of substituted 4-coumarinylpyrano[2,3-c]pyrazole derivatives as potent antibacterial and anti-inflammatory agents

Abstract

A green, eco-friendly and efficient protocol has been developed and synthesized a series of coumarin based pyrano[2,3-c]pyrazole derivatives (3) by multi-component reaction (MCR). Unexpected 3-coumarinyl-3-pyrazolylpropanoic acids (4) have been isolated by the reaction of compound (3) in acidic conditions. Further, intramolecular cyclization of compounds (4) leads to C₄C₄ chromons (9) and these compounds were screened for their biological activities using array of techniques. Most of the compounds exhibited promising antibacterial activity, in particular Gram-positive bacteria. The anti-inflammatory assay was evaluated against protein denaturation as well as HRBC membrane stabilization methods and compounds exhibit excellent anti-inflammatory activity in both methods. Molecular docking study has been performed for all the synthesized compounds with S. aureus dihydropteroate synthetase (DHPS) and results obtained are quite promising.

Keywords: 3-Coumarinyl-3-pyrazolylpropanoic acids; Anti-inflammatory; Antibacterial; C(4)C(4) pyranone; DMAP; Molecular docking; Pyrano[2,3-c]pyrazole; Pyranopyrazolo-pyrimidine.