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

• Published in: Journal of asian natural products research 2008-10, Vol.10 (10), p.957-965
• Main Authors: Liang, Guang, Yang, Shu-Lin, Shao, Li-Li, Zhao, Cheng-Guang, Xiao, Jian, Lv, Yan-Xia, Yang, Ju, Zhao, Yu, Li, Xiao-Kun
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; antibacteria; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; antiinflammation; Bacteria - drug effects; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Cell Line; crystal structure; curcumin analogs; Cyclopentanes - chemical synthesis; Cyclopentanes - pharmacology; Enterobacter cloacae; Enzyme-Linked Immunosorbent Assay; General pharmacology; Macrophages - drug effects; Medical sciences; Mice; Models, Molecular; Molecular Structure; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; synthesis
• ISSN: 1028-6020; 1477-2213
• DOI: 10.1080/10286020802181257

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 1 HNMR 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.