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Licofelone–Nitric Oxide Donors as Anticancer Agents
Author(s) -
Liu Wukun,
Zhou Jinpei,
Liu Yinglin,
Liu Haoran,
Bensdorf Kerstin,
Guo Cancheng,
Gust Ronald
Publication year - 2011
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201000397
Subject(s) - nitric oxide , chemistry , cytotoxicity , nitric oxide synthase , biological activity , pharmacology , cytotoxic t cell , biochemistry , stereochemistry , in vitro , biology , organic chemistry
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.