[Cyclopentadienyl]metalcarbonyl complexes of acetylsalicylic acid as neo-anticancer agents
| Autor: | Ronald Gust, Silke Bergemann, Kerstin Bensdorf, Gerhard Rubner, Anja Wellner, Ingo Ott |
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| Rok vydání: | 2010 |
| Předmět: |
Spectrometry
Mass Electrospray Ionization Magnetic Resonance Spectroscopy Stereochemistry Metabolite medicine.medical_treatment Antineoplastic Agents Cyclopentanes chemistry.chemical_compound Structure-Activity Relationship Cyclopentadienyl complex Cell Line Tumor Drug Discovery medicine Cytotoxic T cell Structure–activity relationship Humans Cyclooxygenase Inhibitors Cytotoxicity Pharmacology chemistry.chemical_classification biology Aspirin Organic Chemistry General Medicine Enzyme chemistry Enzyme inhibitor Cyclooxygenase 2 biology.protein Cyclooxygenase 1 Drug Screening Assays Antitumor Prostaglandin E |
| Zdroj: | European journal of medicinal chemistry. 45(11) |
| ISSN: | 1768-3254 |
| Popis: | [(Prop-2-ynyl)-2-acetoxybenzoate]dicobalthexacarbonyl (Co-ASS), a derivative of the nonsteroidal anti-inflammatory drug aspirin(®) (ASS), demonstrated high cytotoxic potential against various tumor cells. The [acetylene]Co(2)(CO)(6) cluster strongly increased the biological effects compared to aspirin(®). 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 μM) 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. |
| Databáze: | OpenAIRE |
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