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

• Published in: European journal of medicinal chemistry 2017-01, Vol.125, p.101-116
• Main Authors: Chougala, Bahubali M., Samundeeswari, S., Holiyachi, Megharaja, Shastri, Lokesh A., Dodamani, Suneel, Jalalpure, Sunil, Dixit, Sheshagiri R., Joshi, Shrinivas D., Sunagar, Vinay A.
• Format: Article
• Language: English
• Subjects: 3-Coumarinyl-3-pyrazolylpropanoic acids; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - pharmacology; Anti-inflammatory; Anti-Inflammatory Agents - chemical synthesis; Anti-Inflammatory Agents - pharmacology; Antibacterial; C4[sbnd]C4 pyranone; Dihydropteroate Synthase - metabolism; DMAP; Gram-Positive Bacteria - drug effects; Molecular docking; Molecular Docking Simulation; Protein Binding; Pyrano[2,3-c]pyrazole; Pyranopyrazolo-pyrimidine; Pyrazoles - chemical synthesis; Pyrazoles - pharmacology; Staphylococcus aureus - enzymology
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2016.09.021

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. [Display omitted] •One-pot four component green method have been developed and synthesized various coumarin based pyrano[2,3-c]pyrazole derivatives 3 with excellent yield (>90%).•The unexpected 3-coumarinyl-3-pyrazolylpropanoic acids 4 have been isolated from 3 in acidic conditions and intramolecular cyclization of 4 led to C4C4 pyranone or C4C4 chromon 9.•All newly synthesized coumarin based pyrano[2,3-c]pyrazoles are potent antibacterial and anti-inflammatory agents compared to standard.•The molecular docking study of coumarin based pyrano[2,3-c]pyrazole derivatives are well supported for in vitro antibacterial activity.•Among all the synthesized coumarin derivatives, compound 3g and 4b are highly active and more potent in both biological (in vitro) as well as molecular docking simulation studies.