Synthesis and Biological Activities of Transition Metal Complexes Based on Acetylsalicylic Acid as Neo-Anticancer Agents
| Autor: | Gerhard Rubner, Kerstin Bensdorf, Brigitte Kircher, Ronald Gust, Anja Wellner, Silke Bergemann, Ingo Ott |
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| Rok vydání: | 2010 |
| Předmět: |
Stereochemistry
Iron Metabolite chemistry.chemical_element Antineoplastic Agents Apoptosis Isozyme Dinoprostone Ruthenium Structure-Activity Relationship chemistry.chemical_compound Coordination Complexes Cell Line Tumor Drug Discovery Butadienes medicine Humans Cyclooxygenase Inhibitors Prostaglandin E2 Mode of action Cell Proliferation Arachidonic Acid Aspirin Stereoisomerism Cobalt chemistry Biochemistry Cell culture Alkynes Molecular Medicine Arachidonic acid Drug Screening Assays Antitumor Growth inhibition medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 53:6889-6898 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | [(μ(4)-η(2))-(Prop-2-ynyl)-2-acetoxybenzoate]dicobalthexacarbonyl (Co-ASS), a derivative of aspirin (ASS), demonstrated high growth-inhibitory potential against various tumor cells with interference in the arachidonic acid cascade as probable mode of action. The significance of the kind of metal and cluster was verified in this structure-activity study: Co(2)(CO)(6) was respectively exchanged by a tetrameric cobalt-, trimeric ruthenium-, or trimeric ironcarbonyl cluster. Furthermore, the metal binding motif was changed from alkyne to 1,3-butadiene. Compounds were evaluated for growth inhibition, antiproliferative effects, and apoptosis induction in breast (MCF-7, MDA-MB 231) and colon cancer (HT-29) cell lines and for COX-1/2 inhibitory effects at isolated isoenzymes. Additionally, the major COX metabolite prostaglandin E2 (PGE(2)) was quantified in arachidonic acid-stimulated MDA-MB 231 breast tumor cells. It was demonstrated that the metal cluster was of minor importance for effects on cellular activity if an alkyne was used as ligand. Generally, no correlation existed between growth inhibition and COX activity. Cellular growth inhibition and antiproliferative activity at higher concentrations of the most active compounds Prop-ASS-Co(4) and Prop-ASS-Ru(3) correlated well with apoptosis induction. |
| Databáze: | OpenAIRE |
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