Synthesis, structure, and bioevaluation of 2,5-bis(arylmethenyl)cyclopentanones

Abstract

Curcumin is an excellent lead compound with a variety of bioactivity. Recent articles reported that curcumin's instability and low bioavailability in vivo are mainly due to its easily decomposable β-diketone moiety. With the aim of bioactive curcumin analogs with better pharmacokinetic property, we present here 11 bis(arylmethenyl)cyclopentanones similar to curcumin and without β-diketone moiety by reacting relevant arylaldehydes and cyclopentanones. The analogs were structurally determined by ¹HNMR and MS spectra, and the crystal structure of 6 was analyzed by X-ray diffraction. Their antibacterial activities in vitro against seven Gram-positive and Gram-negative bacteria were tested, and their inhibition of TNF-α and IL-6 secretion in LPS-induced mouse macrophages was investigated using enzyme-linked immunosorbent assay. It was observed that several derivatives displayed higher activity when compared with curcumin, and most of the analogs exhibited activities against the ampicillin-resistant Gram-negative Enterobacter cloacae.

Keywords:

• curcumin analogs
• synthesis
• crystal structure
• antibacteria
• antiinflammation

Acknowledgements

This work was supported by the general grant of Zhejiang administration of Chinese Traditional Medicine (2007CA080 and 2007CA079), Wenzhou key research project (S2005B001), and research project of Wenzhou Medical College (89007046), and also by the Zhejiang Department of Education science grant (20070992).