Lipoxin Analogs With Improved Performance

Researchers have synthesized analogs of bioactive lipoxins that appear to improve upon the anti-inflammatory activity of native lipoxins and previously prepared analogs (J. Med. Chem., DOI: 10.1021/jm060270d). Lipoxins are potent anti-inflammatory compounds, and Bayer HealthCare has one of the earlier analogs in development for inflammatory bowel disease. But most lipoxins tend to be rapidly metabolized and inactivated in the body. Patrick J. Guiry of University College Dublin, Ireland, and coworkers have now used Sharpless epoxidation, Heck coupling, and diastereoselective reduction to synthesize a new set of lipoxin analogs (one shown). These analogs retain the carboxyl and hydroxy active region of lipoxins but contain and aromatic ring in the part responsible for metabolic breakdown. They additionally promote clearance of apoptotic leukocytes, an effect that plays a key role in reducing inflammation. The researchers "stabilized a very tricky portion of the molecule, and the analogs show phenomenal retention of biological activity," comments Charles N. Serhan of Harvard Medical School, a member of the team that first isolated lipoxins in 1984.