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),
1H-nuclear magnetic resonance (
1H-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
μg/mL; p < 0.0001) and 15a (MIC = 125 μg/mL; p < 0.001) produced stronger antifungal activity than the
standard drug, ketoconazole (MIC = 25 μg/mL; p < 0.0001) against
P. citrinum
. Compound 4a
displayed higher but moderate activity against Gram-positive bacterium,
S. aureus
(MIC = 100 μg/mL; p
< 0.05) than the standard drug, ofloxacin (MIC = 25 μg/mL; p < 0.0001). Compound 4a also displayed
higher but moderate activity against the Gram-negative bacterium,
E. coli
(MIC = 75 μg/mL; p < 0.0001)
than the standard drug, ofloxacin (MIC = 12.5 μg/mL; p < 0.0001). The structure activity relationship
analysis revealed that the chloro- substitution at position 2 of the phenyl ring along with a chlorobromosubstituted
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.
