title: Synthesis, physicochemical and in vitro pharmacological investigation of new platinum (II) complexes with some cycloalkanespiro-5'-hydantoins.
abstract: Platinum (II) complexes with cyclobutanespiro-5'-hydantoin and cycloheptanespiro-5'-hydantoin were synthesized and evaluated by means of general physicochemical methods. The data from the elemental analysis, IR and NMR spectra suggested the formation of cis-[Pt(C6H8N2O2)2(NH3)2](NO3)2 x 4H2O (PtCBH), when cyclobutanespiro-5'-hydantoin was used as a ligand and cis-[Pt(C9H14N2O2)(NH3)2](NO3)2 x 4H2O (PtCHTH), when cycloheptanespiro-5'-hydantoin was used, respectively. The novel complexes exerted cytotoxic effects at micromolar concentrations against a panel of human tumor cell lines. They were found to trigger apoptosis in HL-60 and BV-173 cells as evidenced by DNA-laddering detection. The evaluation of the effects of PtCBH, PtCHTH and the antineoplastic drugs cisplatin and oxaliplatin against cultured murine kidney epithelial cells revealed that the hydantoin complexes were far less nephrotoxic in vitro.
authors.affiliation: Department of Chemistry, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Street, 1000 Sofia, Bulgaria.
authors.forename: Adriana
authors.initials: A
authors.lastname: Bakalova
authors.forename: Rossen
authors.initials: R
authors.lastname: Buyukliev
authors.forename: Georgi
authors.initials: G
authors.lastname: Momekov
authors.forename: Darvin
authors.initials: D
authors.lastname: Ivanov
authors.forename: Dimitar
authors.initials: D
authors.lastname: Todorov
authors.forename: Spiro
authors.initials: S
authors.lastname: Konstantinov
authors.forename: Margarita
authors.initials: M
authors.lastname: Karaivanova
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003503:Cyclobutanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003508:Cycloheptanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004847:Epithelial Cells; D005562:Formazans / Q000737:chemistry; D018922:HL-60 Cells; D006801:Humans; D006827:Hydantoins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007674:Kidney Diseases / Q000139:chemically induced; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010984:Platinum / Q000737:chemistry; D013055:Spectrophotometry, Infrared; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013778:Tetrazolium Salts / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D003503:Cyclobutanes; D003508:Cycloheptanes; D005562:Formazans; D006827:Hydantoins; D009944:Organoplatinum Compounds; D013141:Spiro Compounds; D013778:Tetrazolium Salts; C079782:MTT formazan; D010984:Platinum