Green, unexpected synthesis of bis-coumarin derivatives as potent anti-bacterial and anti-inflammatory agents

• Published in: European journal of medicinal chemistry 2018-01, Vol.143, p.1744-1756
• Main Authors: Chougala, Bahubali M., Samundeeswari, S., Holiyachi, Megharaja, Naik, Nirmala S., Shastri, Lokesh A., Dodamani, Suneel, Jalalpure, Sunil, Dixit, Sheshagiri R., Joshi, Shrinivas D., Sunagar, Vinay A.
• Format: Article
• Language: English
• Subjects: HRBC membrane; l-proline; Protein denaturation; Pyrano[3,2-c]chromene
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2017.10.072

A green and efficient protocol has been developed and a series of coumarin based pyrano[3,2-c]chromene derivatives (2) have been synthesized using multi-component reaction (MCR) approach. Unexpected 3-coumarinyl-3-pyrazolylpropanoic acids (3) and C4-C4 chromenes (5) have been isolated instead of expected product 4 by the reaction of compound (2) in formic acid at 90 °C for about 4–5 h and at 130 °C for about 8–10 h respectively. Further, C4-C4chromenes (5) formation was confirmed by intramolecular cyclization of compounds (3). These compounds were screened for their biological activities and most of them exhibited promising antibacterial activity. The anti-inflammatory assay was evaluated against HRBC membrane stabilization method and the compounds exhibit excellent anti-inflammatory activity. Molecular docking study has been performed for all the synthesized compounds with Klebsiella pneumoni aeacetolactate synthase and results obtained are quite promising. [Display omitted] •Synthesis of coumarin based pyrano[3,2-c]chromene derivatives were achieved in good to excellent yields underone-pot three component green method.•The unexpected 3-coumarinyl-3-pyrazolylpropanoic acids (3) and C4-C4 chromene derivatives (5) have been isolated by the reaction of compound (2) in acidic conditions.•All the newly synthesized polyfunctionalized coumarin based pyrano[3,2-c]chromenes are potent antibacterial and anti-inflammatory agents compared to standard.•The molecular docking study reveals that, all newly synthesized polyfunctionalized coumarin based pyrano[2,3-c]pyrazoles are well supported for invitro antibacterial activity.