A new series of penta-substituted pyridine derivatives bearing the quinoline nucleus have been synthesized by base-catalyzed cyclocondensation reaction through multi-component reaction (MCR) approach. All the synthesized compounds were subjected to in vitro antimicrobial screening against three Gram positive bacteria (Bacillus subtilis, Clostridium tetani, Streptococcus pneumoniae), three Gram negative bacteria (Escherichia coli, Salmonella typhi, Vibrio cholerae), and two fungi (A. fumigatus, Candida albicans). Reviewing the data, majority of the compounds were found to be active against B. subtilis and C. tetani while the most effective compounds 4c and 4e demonstrated MIC 62.5 lg/ml against V. cholerae and E. coli respectively.