Structure–Activity Relationship Studies of New Sinapic Acid Phenethyl Ester Analogues Targeting the Biosynthesis of 5-Lipoxygenase Products: The Role of Phenolic Moiety, Ester Function, and Bioisosterism

Autor:	Mohamed Touaibia, Diene Codou Faye, Jérémie A. Doiron, Audrey Isabel Chiasson, Sébastien Blanchard, Pierre-Philippe Roy, Marc E. Surette
Rok vydání:	2022
Předmět:	Pharmacology Arachidonate 5-Lipoxygenase Coumaric Acids Neutrophils Organic Chemistry Pharmaceutical Science Esters Phenylethyl Alcohol Analytical Chemistry Structure-Activity Relationship HEK293 Cells Complementary and alternative medicine Drug Discovery Humans Molecular Medicine
Zdroj:	Journal of Natural Products. 85:225-236
ISSN:	1520-6025 0163-3864
DOI:	10.1021/acs.jnatprod.1c00982
Popis:	Sinapic acid is found in many edible plants and fruits, such as rapeseed, where it is the predominant phenolic compound. New sinapic acid phenethyl ester (SAPE) analogues were synthesized and screened as inhibitors of the biosynthesis of 5-lipoxygenase (5-LO) in stimulated HEK293 cells and polymorphonuclear leukocytes (PMNL). Inhibition of leukotriene biosynthesis catalyzed by 5-LO is a validated therapeutic strategy against certain inflammatory diseases and allergies. Unfortunately, the only inhibitor approved to date has limited clinical use because of its poor pharmacokinetic profile and liver toxicity. With the new analogues synthesized in this study, the role of the phenolic moiety, ester function, and bioisosterism was investigated. Several of the 34 compounds inhibited the biosynthesis of 5-LO products, and 20 compounds were 2-11 times more potent than zileuton in PMNL, which are important producers of 5-LO products. Compounds
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0dca0efb9cc68eb2dcdb517eddb34fa9 https://doi.org/10.1021/acs.jnatprod.1c00982 Zobrazit plný text záznamu