Background:
Curcumin, one of the most important pharmacologically significant natural
products, has gained significant consideration among scientists for decades since its multipharmacological
activities. 1, 3-Dicarbonyl moiety of curcumin was found to be accountable for the
rapid degradation of curcumin molecule. The aim of present work is to replace 1, 3-dicarbonyl moiety
of curcumin by pyrazole and phenylpyrazole derivatives with a view to improving its stability and to
investigate the role of substitution in N-phenylpyrazole curcumin on its antibacterial activity against
both Gram-positive as well as Gram-negative bacteria.
Methods:
Pyrazole derivatives of curcumin were prepared by heating curcumin with phenyhydrazine/
substituted phenyhydrazine derivatives in AcOH. The residue was purified by silica gel column
chromatography. Structures of purified compounds were confirmed by 1H NMR and Mass spectroscopy.
The synthesized compounds were evaluated for their antibacterial activity by the microdilution broth
susceptibility test method against gram positive (S. aureus) and gram negative (E. coli).
Results:
Effects of substitution in N-phenylpyrazole curcumin derivatives against S. aureus and E. coli
were studied. The most active N-(3-Nitrophenylpyrazole) curcumin (12) exhibits twenty-fold more potency
against S. aureus (MIC: 10μg/mL)) and N-(2-Fluoroophenylpyrazole) curcumin (5) fivefold more
potency against E. coli (MIC; 50 μg/mL) than N-phenylpyrazole curcumin (4). Whereas, a remarkable
decline in anti-bacterial activity against S. aureus and E. coli was observed when electron donating
groups were incorporated in N-phenylpyrazole curcumin (4). Comparative studies of synthesized compounds
suggest the effects of electron withdrawing and electron donating groups on unsubstituted phenylpyrazole
curcumin (4).
Conclusion:
The structure-activity relationship (SAR) results indicated that the electron withdrawing
and electron donating at N-phenylpyrazole curcumin played key roles for their bacterial inhibitory effects.
The results of the antibacterial evaluation showed that the synthesized pyrazole derivatives of
curcumin displayed moderate to very high activity in S. aureus. In conclusion, the series of novel curcumin
derivatives were designed, synthesized and tested for their antibacterial activities against S. aureus
and E. coli. Among them, N-(3-Nitrophenylpyrazole curcumin; 12) was most active against S. aureus
(Gram-positive) and N-(2-Fluoroophenylpyrazole) curcumin (5) against E. coli (Gram-negative) bacteria.
