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

摘要

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 of aromatic 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 = 8a??32 ?μg/mL) and compound 5g had the most antibacterial activity (range MICs = 16a??256 ?μg/mL). Molecular docking of compounds (5a-i) into fungal 14?±-demethylase and bacterial protein tyrosine phosphatase active sites were also performed and probable binding mode of compounds 5b and 5g were determined.