title: Licofelone-nitric oxide donors as anticancer agents.
abstract: 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.
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan University, Changsha, P.R. China.
authors.forename: Wukun
authors.initials: W
authors.lastname: Liu
authors.forename: Jinpei
authors.initials: J
authors.lastname: Zhou
authors.forename: Yinglin
authors.initials: Y
authors.lastname: Liu
authors.forename: Haoran
authors.initials: H
authors.lastname: Liu
authors.forename: Kerstin
authors.initials: K
authors.lastname: Bensdorf
authors.forename: Cancheng
authors.initials: C
authors.lastname: Guo
authors.forename: Ronald
authors.initials: R
authors.lastname: Gust
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D020030:Nitric Oxide Donors / Q000138:chemical synthesis* / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D020030:Nitric Oxide Donors; D011758:Pyrroles; C088092:licofelone