College of Chemistry and Chemical Engineering, Hunan University, Changsha, P.R. China.
Arch Pharm (Weinheim). 2011 Aug;344(8):487-93. doi: 10.1002/ardp.201000397. Epub 2011 Jun 16.
Five licofelone ([2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-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.
五位利福昔酮（[2,2-二甲基-6-（4-氯苯基）-7-苯基-2,3-二氢-1H-吡咯嗪-5-基]乙酸）一氧化氮供体型化合物通过平行合成方法得到开发。生物筛选表明，利福昔酮与一氧化氮供体之间带有丙基（6b）、丁基（6c）或辛基（6d）链的化合物对 MCF-7 和 MDA-MB-231 乳腺癌以及 HT-29 结肠癌细胞具有高的抗增殖活性。此外，化合物 6b-d 对 MDA-MB-231 细胞的细胞毒性至少比母体化合物利福昔酮高 2 倍，尽管它们对 COX-1 和 COX-2 的抑制活性较低。COX 抑制与生长抑制特性之间没有明显的相关性。然而，化合物产生的高水平一氧化氮可能导致其高细胞毒性活性。
