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Structure-Activity Relationship and Antimicrobial Evaluation of N-Phenylpyrazole Curcumin Derivatives

[ Vol. 16 , Issue. 4 ]

Author(s):

Heli Sanghvi and Satyendra Mishra*   Pages 481 - 488 ( 8 )

Abstract:


Background: Curcumin, one of the most important pharmacologically significant natural products, has gained significant consideration among scientists for decades since its multi-pharmacological activities. 1, 3-Dicarbonyl moiety of curcumin was found to be accountable for the rapid degradation of curcuminmolecule. The aim of present work is to replace 1, 3-dicarbonyl moiety of curcumin by pyrazole and phenylpyrazole derivatives with a viewto improving its stability and to investigate the role of substitution in N-phenylpyrazole curcumin on its antibacterialactivity against both Gram-positive as well as Gram-negative bacteria.

Methods:Pyrazole derivatives of curcumin were prepared by heating curcumin with phenyhydra-zine/substituted phenyhydrazinederivatives 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 microdilutionbroth 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. coliwere studied.The most active N-(3-Nitrophenylpyrazole) curcumin (12) exhibits twenty-foldmore po-tency against S. aureus (MIC: 10μg/mL))andN-(2-Fluoroophenylpyrazole) curcumin (5) fivefold more potency against E. coli(MIC; 50 μg/mL) than N-phenylpyrazole curcumin (4).Whereas, a remarkabledecline in anti-bacterialactivity against S. aureus and E. coli was observed whenelectron donating groups were incorporated in N-phenylpyrazole curcumin (4). Comparative studies of synthesized com-pounds suggest the effects of electron withdrawing and electron donating groups on unsubstituted phe-nylpyrazole curcumin (4).

Conclusion:The structure-activityrelationship (SAR) results indicated that the electron withdrawing and electron donating at N-phenylpyrazole curcumin played key roles for their bacterial inhibitory ef-fects. 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 cur-cumin derivatives were designed, synthesized and tested for their antibacterial activities against S. aure-us and E. coli. Among them, N-(3-Nitrophenylpyrazole curcumin; 12) wasmost active against S. aureus(Gram-positive) and N-(2-Fluoroophenylpyrazole) curcumin (5) against E. coli(Gram-negative) bacte-ria.

Keywords:

Curcumin, Pyrazole Derivatives of curcumin, Antibacterial Agent, Staphylococcus aureus, E. coli.

Affiliation:

Medicinal Chemistry Laboratory, Centre for Engineering and Enterprise, Institute of Advanced Research, Koba Institu-tional, Area Gandhinagar, Gujarat, 382426, Medicinal Chemistry Laboratory, Centre for Engineering and Enterprise, Institute of Advanced Research, Koba Institu-tional, Area Gandhinagar, Gujarat, 382426



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