Synthesis of Novel 1-(3′-CHLORO-1′,4′-DIOXO-1′,4′-Dihydronaphthalen-2′-YL)-5-Substitued-1H-Pyrimidine-2,4-Dione as Potential Antibacterial Agents

A series of new pyrimidine analogs carrying 1,4-naphthoquinone and uracil moiety were prepared as hybrid compounds 1-(3 -chloro-1 ,4 -dioxo-1 ,4 -dihydronaphthalen-2 -yl)-5-substitued-1H-pyrimidine-2,4-diones (6 – 9), which might possess biological activity. The structures of new products were confirmed by IR, 1 H and 13 C NMR, and mass spectroscopy data. All synthesized compounds were also evaluated for their antibacterial activity. The structure – activity relationship for these compounds was studied and the results showed that 1-(3 -chloro-1 ,4 -dioxo-1 ,4 -dihydronaphthalen-2 -yl)-5-fluoro-1H-pyrimidine-2,4-dione (9) containing a fluorine atom exhibited in vitro potent antibacterial activity (MIC 50 = 1.0 μg/mL) comparable with that of the clinically useful antibacterial drug gentamicin (MIC 50 = 2.0 g/mL) against S. aureus and B. subtilis. Compound 9 also exhibited the same antibacterial activity with MIC 50 = 1.0 mg/mL compared to gentamicin and ciprofloxacin against P. aeruginosa and with MIC 50 = 0.5 mg/mL compared to Gentamicin (MIC 50 = 0.5 mg/mL) against E. coli.