Pyridine clubbed coumarin analogues: Their synthesis and biological studies as antimicrobials and antioxidants

Abstract

The major aim of this study is to develop the new class of coumarin candidate clubbed with dihydropyridine-3-carbonitrile with an improved potency as an antimicrobial and antioxidant agent. The key intermediate 6-nitro-4-methyl coumarin-yl chloro acetate 5 have been linked to the 6-(4-fluorophenyl)-2-oxo-4-phenyl-1,2-dihydro pyridine-3-carbonitrile IIa-j derivative to afford 4-methyl-6-nitro-2-oxo-2H-chromen-7-yl-2-(3-cyano-6-(4-fluoro phenyl)-4-(substituted-phenyl) pyridin-2-yl-oxy) acetates 7a-j via efficient organic transformations. All the new derivatives have been characterized by spectral studies (IR, ¹H and ¹³C NMR and mass spectroscopy). In vitro antimicrobial activity have been carried out using the broth microdilution method and antioxidant potency using DPPH bioassays. Bioassay results reveal that compound 7e are equipotent against E. coli with MIC value 50 µg/ mL compared to standard drug ciprofoloxacin. A final analogue 7c with 4-chlorophenyl substituent indicated better antifungal potency against C. albicans with MIC value 100 µg/ mL compared to standard drug griseofulvin. In addition, newly synthesized analogues have been found to be significant scavengers of DPPH radical with IC₅₀ values of 32.11 μg/mL. It has been observed that the potent antibacterial candidate has proved to possess significant antioxidant activity. The presence of chlorine and hydroxy group on phenyl ring plays an important role for the potency in above mentioned biological assay.