Design, Synthesis, Biological Evaluation and Molecular Modeling Study of Novel Indolizine-1-Carbonitrile Derivatives as Potential Anti-Microbial Agents

A novel one-pot two step tandem reaction for the synthesis of indolizine-1-carbonitrile derivatives (5a-i) was identified. the route comprises 1,3-dipolar cycloaddition reaction ofaromatic aldehyde derivatives (1a-i), malononitrile (2) and 1-(2-(4-bromophenyl)-2-oxoethyl)-2-chloropyridin-1-ium (4) under ultrasound irradiation at room temperature in the presence of triethylamine at acetonitrile. the product compounds were tested against bacteria and fungi. it was revealed that compound 5b had the most antifungal activity (range mics = 8–32 µg/ml) and compound 5g had the most antibacterial activity (range mics = 16–256 µg/ml). moleculardocking of compounds (5a-i) into fungal 14α-demethylase and bacterial protein tyrosinephosphatase active sites were also performed and probable binding mode of compounds 5b and 5g were determined.