Licofelone–Nitric Oxide Donors as Anticancer Agents

✍ Scribed by Wukun Liu; Jinpei Zhou; Yinglin Liu; Haoran Liu; Kerstin Bensdorf; Cancheng Guo; Ronald Gust

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 250 KB
• Volume: 344
• Category: Article
• ISSN: 0365-6233
• DOI: 10.1002/ardp.201000397

✦ Synopsis

Abstract

Five licofelone ([2,2‐dimethyl‐6‐(4‐chlorophenyl)‐7‐phenyl‐2,3‐dihydro‐1__H__‐pyrrolizin‐5‐yl]acetic acid) nitric oxide donor conjugates were developed by a parallel synthesis approach. The biological screening revealed that compounds with a propyl (6b), butyl (6c), or octyl (6d) chain between licofelone and the nitric oxide donor exhibited high antiproliferative potency at MCF‐7 and MDA‐MB–231 breast cancer as well as at HT‐29 colon cancer cells. Moreover, 6b–d possessed at least 2‐fold higher cytotoxicity at MDA‐MB‐231 cells than the parent compound licofelone although they showed less inhibitory activity at COX‐1 and COX‐2. A correlation between COX inhibition and growth inhibitory properties is not visible. However, the high levels of nitric oxide production of the compounds may result in their high cytotoxic activity.