Abstract
•Novel nicotinonitriles-bearing various substituent at positions 2, 4, and 6 have been synthesized under microwave reaction conditions.•Yields under microwave irradiation increased with 1.19% when compared with conventional method.•Ester derivatives for nicotinonitrile derivatives 15 and 16 shown excellent antimicrobial activity.•Molecular modeling study for tested compounds with binding energy of −9.5 kcal/mol for predicting novel effective antibacterial.
A series of new nicotinonitrile derivatives 3–18 bearing substituents at positions 2, 4, and 6 are prepared under microwave reaction conditions. The higher yields were obtained in a shorter time under microwave irradiation with a percentage of 1.19% when compared with conventional method. All the newly synthesized molecular structures are elucidated via spectral techniques. The in vitro antimicrobial properties for all newly prepared derivatives were performed. The results obtained showed that new nicotinonitrile derivatives Ethyl 2-((3-cyano-6-(2,4-dichlorophenyl)-4-(3,4-dichlorophenyl)pyridin-2-yl)oxy) acetate (15) and Ethyl 2-((4-(4-bromophenyl)-3-cyano-6-(2,4-dichlorophenyl)pyridin-2-yl)oxy)acetate (16); which bearing ester substituent at position 2 for nicotinonitrile ring displayed excellent antimicrobial activity. Moreover, a computational molecular modeling study was initiated with an average least binding energy of −9.5 kcal/mol to support the assumed mode of action for tested compounds and optimize a reliable model for predicting novel effective antibacterial.