title: Synthesis, characterisation and biological evaluation of copper and silver complexes based on acetylsalicylic acid.
abstract: Metalcarbonyl complexes with ligands derived from acetylsalicylic acid demonstrated high cytotoxic potential against various tumor cell lines and strong inhibition of the cyclooxygenase enzymes COX-1 and 2. In this study we tried to achieve comparable effects with [alkyne]silver or copper trifluoromethanesulfonate complexes which are more hydrophilic then the uncharged metalcarbonyl derivatives. All compounds were evaluated for growth inhibition against breast (MCF-7, MDA-MB 231) and colon cancer (HT-29) cell lines and for COX-1 and COX-2 inhibitory effects at isolated isoenzymes. Pure ligands showed neither cytotoxic nor COX-inhibitory effects. While the silver complexes of (but-2-ynyl)-2-acetoxybenzoate (But-ASS-Ag) and (but-2-yne-1,4-diyl)-bis(2-acetoxybenzoate) (Di-ASS-But-Ag) were strong cytostatics, only the copper complex Di-ASS-But-Cu was active. At the COX enzymes the complexes were more effective than their ligands and aspirin.
authors: Institute of Pharmacy, Freie Universität Berlin, Germany.
authors: Gerhard
authors: G
authors: Rubner
authors: Kerstin
authors: K
authors: Bensdorf
authors: Anja
authors: A
authors: Wellner
authors: Silke
authors: S
authors: Bergemann
authors: Ronald
authors: R
authors: Gust
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001241:Aspirin / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000737:chemistry*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012834:Silver / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D009942:Organometallic Compounds; D012834:Silver; D003300:Copper; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D001241:Aspirin