Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 45, Issue 11, Pages 5157-5163Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2010.08.028
Keywords
Transition metal complexes; Acetylsalicylic acid; Cyclopentadiene; Cytotoxicity; COX inhibition
Categories
Funding
- DFG - Deutsche Forschungsgemeinschaft [FOR 630]
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[(Prop-2-ynyl)-2-acetoxybenzoate]dicobalthexacarbonyl (Co-ASS), a derivative of the nonsteroidal anti-inflammatory drug aspirin (R) (ASS), demonstrated high cytotoxic potential against various tumor cells. The [acetylene]Co-2(CO)(6) cluster strongly increased the biological effects compared to aspirin (R). In this study we evaluated the use of [cyclopentadienyl]metalcarbonyl as cytotoxic moiety with a broader series of metals: molybdenum, manganese, cobalt and rhodium. All compounds were tested for cytotoxicity against breast (MCF-7, MDA-MB-231) and colon cancer (HT-29) cell lines. Their COX-1 and COX-2 inhibitory effects were evaluated at isolated isoenzymes. Additionally, the influence on the level of the major COX metabolite prostaglandin E-2 (PGE(2)) was quantified in MDA-MB-231 breast cancer cells. Whereas the pure ligands or ASS did not show any cytotoxic effect, all metal complexes inhibited the tumor cell growth. The inhibitory effects at COX-1 and COX-2 enzymes were low. Only the Prop-Cp-ASS-Rh complex (10 mu M) caused an important inhibition of COX-1 by 60% and COX-2 by 30%. ASS showed at the same concentration only a marginal repression of COX-1 activity (30%) and no effect on COX-2. (C) 2010 Elsevier Masson SAS. All rights reserved.
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