Bioorganic & medicinal chemistry | 2019
Convenient framework of poly functionalized (E)-2-benzylideno-(Z)-carbazolylideno cyanoacetamides via rearrangements as an efficient antibiofilm inhibitors with SAR study.
Abstract
A simple and one-pot approach for the synthesis of highly functionalized novel (E)-2-benzylideno-(Z)-carbazolylideno cyanoacetamide derivatives from different 2-(2 ,3 ,4 ,9 -tetrahydro-carbazol-1 -ylidene)-propanedinitriles and aryl/heteroaryl carbaldehydes via vinylogous aldol reaction. The structures of the molecules were designated by FT-IR, 1H NMR, 13C NMR studies, elemental and X-ray crystallographic analysis. The synthesized pure products have been screened for in vitro antibiofilm inhibitory activity towards antibiotic-resistant pathogenic organisms. All the synthesized compounds showed biofilm inhibition. Promisingly, the moieties 3a, 3d and 3h showed higher antibiofilm activity at biofilm inhibitory concentration (BIC) (200\u202fμg/mL) against bacterial pathogens. Among the three moieties, 3a showed high prospective against E. coli biofilm with minimal and maximal BIC percentage of 32% (10\u202fμg/mL) and 89% (100\u202fμg/mL) and chosen lowest BIC for further evaluation. Also, the 3a generate ROS two fold at 1\u202fh treatment in E. coli biofilm. The 3a exhibited no toxic effect on cell viability upto 75\u202fμg/mL in HEK293 cell lines. The results of the present study reveal that among (E)-2-benzylideno-(Z)-carbazolylideno cyanoacetamides, (E)-2-benzylideno-6-methyl-2,3,4,9-tetrahydro-1H-carbazol-(Z)-α-carbamino-α-cyano-1-ylidene (3a) could be exploited as an excellent antibiofilm agent against carbapenem-resistant E. coli bacteria strains.