A facile one pot synthesis of novel pyrimidine derivatives of 1,5-benzodiazepines via domino reaction and their antibacterial evaluation

A new series of pyrimidine (8, 14, 18 and 23) embellished analogues of 1,5-benzodiazepines were synthesized by the one-pot domino approach using the catalyst DABCO (1,4-diazabicyclo[2.2.2]octane). For each compound synthesized, anti-microbial efficacy was determined using broth microdilution assay and half maximal inhibitory concentration (IC50). Furthermore, FESEM (Field emission scanning electron microscope) studies were also carried out to observe the effect of the structure of test compounds on the morphology of both Gram-positive (S. aureus) and Gram-negative (E. coli) cell walls. The leakage of nucleotides and their integral components from compromised bacterial cells was assessed by plotting the optical density (OD) with respect to time of exposure at 320 nm. Anti-bacterial studies revealed that compound 23 was most active against targeted bacterial species. Results of the antibacterial study indicated that all the test compounds possess significant antibacterial potential against targeted bacterial strains. Amongst all, in the FE-SEM study, compound 23 caused marked alteration in bacterial cell morphology and resulted in maximum leakage of cell nucleotides in bacterial strains as compared to controls. Further efforts are required to establish their efficacy as antibacterial agents in clinical management. One-pot domino approach was used to synthesize novel pyrimidine embellished analogues of 1,5-benzodiazepine (8, 14, 18 and 32). Structure of all compounds was established through IR, 1H NMR, 13C NMR, and mass spectral data. Further, antibacterial activity, FE-SEM imaging, and cell leakage study were also performed. [Display omitted] •One-pot domino method has been used to synthesize novel pyrimidine compounds.•Synthesized compounds were analyzed using NMR, IR, MS and Fe-SEM.•Pyrimidine compounds showed excellent antibacterial properties and maximum leakage of cell nucleotides.