Title:Omega-3 Polyunsaturated Fatty Acid Derived Lipid Mediators and their Application in Drug Discovery
Volume: 27
Issue: 10
关键词:
多不饱和脂肪酸，脂质介体，脂蛋白，omega-3，生物转化，药物设计策略。
摘要: 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.
