Synthesis and biological evaluation of curcumin analogues without the beta‐diketone moiety

Abstract

Curcumin is an excellent lead compound with a variety of biological activities. However, its potential beneficial effects are limited due to its instability and low bioavailability in vivo. It is believed that presence of the beta‐diketone moiety attributes to the instability of curcumin under physiological condition, poor absorption and fast metabolism. In the present study, a series of curcumin analogues with more stable structures and better biological properties were synthesized. Methods: Curcumin analogues without the beta‐diketone moiety were synthesized by reacting relevant arylaldehydes and cyclopentanone in alkaline condition. The structures were determined by HNMR and MS. The crystal structures were analyzed by X‐ray diffraction. The antibacterial activities against seven Gram‐positive and Gram‐negative bacteria were tested in vitro and anti‐inflammatory activates were examined by measuring the inhibitory effect on LPS‐induced TNF‐alfa and IL‐6 expression in macrophages using ELSA. Results: Most of the analogues exhibited inhibitory activity against the ampicillin‐resistant Gram‐Enterobacter cloacae. Several analogues displayed better anti‐bacterial and anti‐inflammatory activities compared to curcumin. Conclusion: The properties and position of the substituent and the space of the linking strain determine the anti‐bacterial and anti‐inflammatory activities.