2. Academic Validation
  3. Investigations on cytotoxicity and anti-inflammatory potency of licofelone derivatives

Investigations on cytotoxicity and anti-inflammatory potency of licofelone derivatives

  • Eur J Med Chem. 2011 Mar;46(3):907-13. doi: 10.1016/j.ejmech.2011.01.002.
Wukun Liu 1,  Jinpei Zhou,  Kerstin Bensdorf,  Huibin Zhang,  Haoran Liu,  Yubin Wang,  Hai Qian,  Yanchun Zhang,  Anja Wellner,  Gerhard Rubner,  Wenlong Huang,  Cancheng Guo,  Ronald Gust
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, China Pharmaceutical University, Tongjia Xiang 24, 210009 Nanjing, PR China.
PMID: 21295381 DOI: 10.1016/j.ejmech.2011.01.002
Abstract

A series of C5-substituted licofelone ([2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl]acetic acid) derivatives were developed by a parallel synthesis approach and investigated for cytotoxicity against MCF-7 and MDA-MB-231 cells as well as for anti-inflammatory potency in vitro and in vivo. Dependent on the C5-substituent, the compounds showed high selectivity for MCF-7 cells. Especially 2-oxoethyl benzoate derivatives were inactive at the MDA-MB-231 cell line and as active as 5-FU at MCF-7 cells. C5-acetyl (8a), -2-oxoethyl formiate (8e), -2-oxoethyl acetate (8f) and -2-oxoethyl propionate (8g) derivatives showed growth inhibition at both cell lines, comparable with cisplatin. Modifications significantly reduced the inhibitory potency at COX-1 and COX-2 in vitro and in the xylene-induced ear swelling assay in mice. Only compound 8a was equipotent to licofelone, ibuprofen and celecoxibe in vivo.

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