Journal
FUTURE MEDICINAL CHEMISTRY
Volume 1, Issue 1, Pages 179-200Publisher
FUTURE SCI LTD
DOI: 10.4155/FMC.09.15
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Funding
- Division Of Chemistry
- Direct For Mathematical & Physical Scien [0847262] Funding Source: National Science Foundation
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Background: The nuclear transcription factor NF-kappa B 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-kappa B and have played an integral role in identifying implicated pathways. Prominent among them are the sesquiterpene lactones, polyphenolic enones and other alpha,beta-unsaturated carbonyl-containing molecules, particularly alpha-methylene-gamma-butyrolactones. Discussion: This mini-review provides an introductory overview of some of the associated pathways involving NF-kappa B in cancer and discusses the structures and mode of action of natural alpha,beta-unsaturated carbonyl-containing inhibitors and their synthetic counterparts. A review of the recent methods for the synthesis of alpha-alkylidene-gamma-butyrolactones is also provided, with the aim of arousing the interest of synthetic chemists for the design and development of novel NF-kappa B inhibitors. Conclusions: Modulating damaging effects without harming the inflammatory and immune responses are crucial parameters for developing NF-kappa B inhibitors. Examination of novel alpha,beta-unsaturated carbonyls and the further discovery of simple methods to prepare such molecules should lead to the identification of site-specific inhibitors.
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