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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

General Review Article

Omega-3 Polyunsaturated Fatty Acid Derived Lipid Mediators and their Application in Drug Discovery

Author(s): Curtis W. Pazderka, Brian Oliver, Michael Murray and Tristan Rawling*

Volume 27, Issue 10, 2020

Page: [1670 - 1689] Pages: 20

DOI: 10.2174/0929867325666180927100120

Price: $65


Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) play crucial and often opposing regulatory roles in health and in pathological conditions. n-3 and n-6 PUFA undergo biotransformation to parallel series of lipid mediators that are potent modulators of many cellular processes. A wide range of biological actions have been attributed to lipid mediators derived from n-6 PUFA, and these mediators have served as lead compounds in the development of numerous clinically approved drugs, including latanoprost (Xalatan: Pfizer), which is listed on the WHO Model List of Essential Medicines. n-3 PUFA-derived mediators have received less attention, in part because early studies suggested that n-3 PUFA act simply as competitive substrates for biotransformation enzymes and decrease the formation of n-6 PUFA-derived lipid mediators. However, more recent studies suggest that n-3 PUFA-derived mediators are biologically important in their own right. It is now emerging that many n-3 PUFA-derived lipid mediators have potent and diverse activities that are distinct from their n-6 counterparts. These findings provide new opportunities for drug discovery. Herein, we review the biosynthesis of n-3 PUFA-derived lipid mediators and highlight their biological actions that may be exploited for drug development. Lastly, we provide examples of medicinal chemistry research that has utilized n-3 PUFA-derived lipid mediators as novel lead compounds in drug design.

Keywords: Polyunsaturated fatty acids, lipid mediators, oxylipin, omega-3, biotransformation, drug design strategies.

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