Metal-Free Based Domino Approach to Pyrano-Fused-Pyrido[3,2,1-jk]carbazolones: Antibacterial and Molecular Docking Studies

Abstract

A facile, metal-free based one-pot annulation reaction of several Morita-Baylis-Hillman acetates of MVK/acrylate with 4-hydroxy-6H-pyrido[3,2,1-jk]carbazol-6-one as C/O-1,3-binucleophile promoted by DABCO as an organobase in 2-MeTHF at room temperature is reported. This environmentally benign method delivers a family of pyrano-fused pyridocarbazolones in high yields with medium to good diastereoselectivities under mild conditions. Antibacterial studies showed that attaching carboxylate group on pyran ring of pyrano-fused pyridocarbazolones has shown better activities (MIC up to ≥6.25 μg/mL) as compared to acetyl one. Interestingly, incorporation of several substituents namely CF3, NO2, MeO, F, Cl and Br on the aryl rings of pyridocarbazolones carboxylates sharply enhanced the antibacterial activities which make them more potent or equipotent than commercial antibiotic ofloxacin. Furthermore, in silico docking studies indicated that MolDock scores of trans-isomers with E. coli protein are in general higher than cis-isomers which are in good agreement with their observed in vitro antibacterial activities. © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim