Design, synthesis and bioactions of novel stable mimetics of lipoxins and aspirin-triggered lipoxins

Nicos A. Petasis, Irini Akritopoulou-Zanze, Valery V. Fokin, Giovanni Bernasconi, Raquel Keledjian, Rong Yang, Jasim Uddin, Kalyan C. Nagulapalli, Charles N. Serhan

Research output: Contribution to journalReview article

49 Citations (Scopus)

Abstract

The lipoxins (LX) are a class of potent endogenous oxygenated products that are enzymatically generated from arachidonic acid and have novel anti-inflammatory properties and promote resolution. Elucidation of the biochemical pathways involved in the metabolic inactivation of LX and the discovery of the aspirin-triggered lipoxins (ATL) provided the basis for the design and synthesis of stable analogs of LX and ATL. This special issue review describes the efforts that led to the design and synthesis of stable LX/ATL mimetics, which permitted the detailed elucidation of their novel biological roles, leading to the development of new anti-inflammatory agents that mimic their actions. These synthetic molecules provided the means to uncover the physiologic roles of both the LX and the ATL biosynthetic pathways which led to several unexpected discoveries. Among these findings is the involvement of polyisoprenyl phosphates (PIPP) in intracellular signaling mediated by presqualene diphosphate (PSDP), and the recognition of the novel roles of these lipid mediators in regulating cell trafficking during inflammation as well as in promoting resolution of inflammatory processes. These efforts also provided the basis for examining the potential therapeutic role of LX/ATL stable mimetics and led to the development of new analogs with improved pharmacokinetics that opened the way to potentially new approaches to treating human diseases.

Original languageEnglish
Pages (from-to)301-321
Number of pages21
JournalProstaglandins Leukotrienes and Essential Fatty Acids
Volume73
Issue number3-4
DOIs
Publication statusPublished - Sep 2005
Externally publishedYes

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ASJC Scopus subject areas

  • Clinical Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Petasis, N. A., Akritopoulou-Zanze, I., Fokin, V. V., Bernasconi, G., Keledjian, R., Yang, R., Uddin, J., Nagulapalli, K. C., & Serhan, C. N. (2005). Design, synthesis and bioactions of novel stable mimetics of lipoxins and aspirin-triggered lipoxins. Prostaglandins Leukotrienes and Essential Fatty Acids, 73(3-4), 301-321. https://doi.org/10.1016/j.plefa.2005.05.020