Investigations on cytotoxicity and anti-inflammatory potency of licofelone derivatives
| Autor: | Jinpei Zhou, Gerhard Rubner, Yanchun Zhang, Haoran Liu, Kerstin Bensdorf, Hai Qian, Can-Cheng Guo, Huibin Zhang, Ronald Gust, Wenlong Huang, Yubin Wang, Wukun Liu, Anja Wellner |
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| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.drug_class Cell Survival Anti-Inflammatory Agents Antineoplastic Agents Breast Neoplasms Anti-inflammatory chemistry.chemical_compound Mice In vivo Cell Line Tumor Drug Discovery medicine Potency Animals Edema Cyclooxygenase Inhibitors Pyrroles Cytotoxicity Pharmacology Organic Chemistry General Medicine In vitro chemistry Biochemistry Cell culture Female Growth inhibition Licofelone |
| Zdroj: | European journal of medicinal chemistry. 46(3) |
| ISSN: | 1768-3254 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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