title: Synthesis, characterization and biological activity of Pt(II) and Pt(IV) complexes with 5-methyl-5(4-pyridyl)-2,4-imidazolidenedione.
abstract: New platinum(II) and platinum(IV) complexes with 5-methyl-5(4-pyridyl)-2,4-imidazolidenedione and various halogen ions with general formula [PtL(2)X(2)] and [PtL(2)Cl(4)], where L is the organic ligand and X is Cl(-), Br(-), J(-), were synthesized. The molecular formulae of all the complexes were confirmed by elemental analysis, IR, (1)H, (13)C NMR spectral analyses and molar conductivity. The cytotoxic effects of these complexes were examined on some human tumor cell lines. The newly synthesized cis-[PtL(2)Cl(2)] exerted cytotoxic activity against SKW-3, MCF-7, EJ, U-266 tumor cell lines, while cis-[PtL(2)Br(2)], trans-[PtL(2)I(2)] were less active. The higher oxidation state complex cis-[PtL(2)Cl(4)] was inactive in all cell lines but in SKW-3 some augmentation of the cytotoxicity was seen after co-administration of ascorbic acid but not when treated in combination with reduced glutathione or N-acetylcysteine. A DNA-fragmentation analysis revealed that the cytotoxicity of the dichloro analogue, characterized with superior activity compared to the other complexes, is mediated by induction of apoptotic cell death.
authors: Department of Chemistry, Faculty of Pharmacy, Medical University-Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria. adrigebk@abv.bg
authors: Adriana
authors: A
authors: Bakalova
authors: Hristo
authors: H
authors: Varbanov
authors: Rossen
authors: R
authors: Buyukliev
authors: Georgi
authors: G
authors: Momekov
authors: Dilyan
authors: D
authors: Ferdinandov
authors: Spiro
authors: S
authors: Konstantinov
authors: Darvin
authors: D
authors: Ivanov
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002648:Child; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D048288:Imidazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010984:Platinum; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002614:Chelating Agents; D048288:Imidazolines; D011725:Pyridines; D010984:Platinum