Synthesis and Evaluation of Antimicrobial Activity of Some 2-Morpholinomethylamino-4-(7-Unsubstituted/Substituted Coumarin-3-yl)-6-Chlorosubstitutedphenyl Pyrimidines

Purpose: To prepare some 2-morpholinomethylamino-4-(7-unsubstituted/substitutedcoumarin-3-yl)-6-chlorosubstitutedphenyl pyrimidines as antimicrobial agents. Methods: Some 2-morpholinomethylamino-4-(7-unsubstituted/substitutedcoumarin-3-yl)-6-chlorosubstitutedphenyl pyrimidines were prepared by reacting 2-amino-4-(7-substituted/unsubstituted coumarin-3-yl)-6-(chlorosubstitutedphenyl) pyrimidines with morpholine and formaldehyde. The chemical structures of the synthesized compounds were elucidated by their Fourier Transform infra-red (FTIR), H-1-nuclear magnetic resonance (H-1-NMR) and mass spectra, as well as by elemental analysis. These compounds were investigated for their antimicrobial activity against ten bacteria and five fungi by serial plate dilution method using the standard drugs, ofloxacin and ketoconazole, respectively, and their minimum inhibitory concentrations (MICs) were determined. Results: A total of eighteen new compounds (1a-18a) were synthesized. Compound 3a (MIC = 75 mu g/mL; p < 0.0001) and 15a (MIC = 125 mu g/mL; p < 0.001) produced stronger antifungal activity than the standard drug, ketoconazole (MIC = 25 mu g/mL; p < 0.0001) against P. citrinum. Compound 4a displayed higher but moderate activity against Gram-positive bacterium, S. aureus (MIC = 100 mu g/mL; p < 0.05) than the standard drug, ofloxacin (MIC = 25 mu g/mL; p < 0.0001). Compound 4a also displayed higher but moderate activity against the Gram-negative bacterium, E. coli (MIC = 75 mu g/mL; p < 0.0001) than the standard drug, ofloxacin (MIC = 12.5 mu g/mL; p < 0.0001). The structure activity relationship analysis revealed that the chloro-substitution at position 2 of the phenyl ring along with a chlorobromo-substituted coumarin moiety of the synthesized compounds is critical for activity against Gram-positive bacteria, Gram negative bacteria and fungi. Conclusion: The synthesized compounds are relatively active antifungal agents but are weak antibacterial agents. However, they require further evaluation of their antifungal activity against other fungal strains to ascertain their broad spectrum activity.