Natural and synthetic α,β-unsaturated carbonyls for NF-κB inhibition.

BACKGROUND: The nuclear transcription factor NF-κB has gained considerable importance due to its major involvement in inflammation and constitutive activity in malignant cells. It is induced by a variety of stimuli and controls the expression of several proteins involved in biological processes. Numerous natural products and synthesized organic molecules have been reported to inhibit NF-κB and have played an integral role in identifying implicated pathways. Prominent among them are the sesquiterpene lactones, polyphenolic enones and other α,β-unsaturated carbonyl-containing molecules, particularly α-methylene-γ-butyrolactones. DISCUSSION: This mini-review provides an introductory overview of some of the associated pathways involving NF-κB in cancer and discusses the structures and mode of action of natural α,β-unsaturated carbonyl-containing inhibitors and their synthetic counterparts. A review of the recent methods for the synthesis of α-alkylidene-γ-butyrolactones is also provided, with the aim of arousing the interest of synthetic chemists for the design and development of novel NF-κB inhibitors.
CONCLUSIONS: Modulating damaging effects without harming the inflammatory and immune responses are crucial parameters for developing NF-κB inhibitors. Examination of novel α,β-unsaturated carbonyls and the further discovery of simple methods to prepare such molecules should lead to the identification of site-specific inhibitors.