title: [Cyclopentadienyl]metalcarbonyl complexes of acetylsalicylic acid as neo-anticancer agents.
abstract: [(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.
authors.affiliation: Institute of Pharmacy, Freie Universität Berlin, Königin-Luise-Str. 2 + 4, 14195 Berlin, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rubner
authors.forename: Kerstin
authors.initials: K
authors.lastname: Bensdorf
authors.forename: Anja
authors.initials: A
authors.lastname: Wellner
authors.forename: Silke
authors.initials: S
authors.lastname: Bergemann
authors.forename: Ingo
authors.initials: I
authors.lastname: Ott
authors.forename: Ronald
authors.initials: R
authors.lastname: Gust
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001241:Aspirin / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D051545:Cyclooxygenase 1 / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D003517:Cyclopentanes / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D003517:Cyclopentanes; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D001241:Aspirin