title: Cytotoxic and antimicrobial activities of Cu(II), Co(II), Pt(II) and Zn(II) Complexes with N,O-chelating heterocyclic carboxylates.
abstract: A series of Cu(II), Co(II), Pt(II) and Zn(II) coordination compounds has been prepared by the reaction of the metal chlorides with pyrazine-2-carboxylic acid, pyridine-2-carboxylic acid, imidazole-4-carboxylic acid, benzimidazole-2-carboxylic acid and 1-methylimidazole-2-carboxylic acid. The complexes were characterized by IR, UV-VIS, elemental analysis, and some by (1) H-NMR, X-ray crystallography, HPLC and LC/MS spectroscopy. All complexes consist of a 2:1 ratio of ligand to metal ion. IR and X-ray crystallography show that coordination is through the nitrogen and carboxylate oxygen donor atoms of the ligand to form chelating rings. DFT calculations predict that the trans-coordinated isomers are thermodynamically more stable than their cis-forms. Only one of five complexes studied by X-ray crystallography, Cu(II) complex of 1-methylimidazole-2-carboxylic acid showed a cis-configured metal ion center. HPLC analysis indicated that Pt(II) complex of 1-methylimidazole-2-carboxylic acid is dominated (>90%) by the trans-configured complex. All other complexes showed one isomer, presumably the trans-form. The cytotoxic activity was investigated in human cancer cell lines in vitro; only the Pt(II) complexes were active. The antimicrobial activity against four bacterial strains and one fungi was estimated by the MIC method and best results were found amongst the Co(II) complexes. These results indicate that trans-coordinated bischelating N,O-heterocyclic carboxylates of Pt(II) are an interesting new class of potential antitumor agents.
authors.affiliation: Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Ernst-Moritz-Arndt University of Greifswald, Germany.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Buczkowska
authors.forename: Anja
authors.initials: A
authors.lastname: Bodtke
authors.forename: Ulrike
authors.initials: U
authors.lastname: Lindequist
authors.forename: Maria
authors.initials: M
authors.lastname: Gdaniec
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Bednarski
mesh_terms: D000147:Acids, Heterocyclic / Q000138:chemical synthesis / Q000737:chemistry; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000737:chemistry; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000737:chemistry; D003035:Cobalt / Q000737:chemistry; D003300:Copper / Q000737:chemistry; D006801:Humans; D008670:Metals / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010984:Platinum / Q000737:chemistry; D015032:Zinc / Q000737:chemistry
chemical_list: D000147:Acids, Heterocyclic; D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D002614:Chelating Agents; D008670:Metals; D009942:Organometallic Compounds; D003035:Cobalt; D010984:Platinum; D003300:Copper; D015032:Zinc