title: Synthesis, physicochemical investigation and cytotoxic activity of new Pt(II) complexes with hydantoin ligands.
abstract: The interaction of cis-dichlorodiaminplatinum(II) (cis-DDP) with 2,4-imidazolidenedione-5-methyl-5-phenyl was studied. The method of preparation of the new Pt(II) complex consisted in precipitation of chloride ions from cis-DDP via a diaqua complex and reaction with the ligand in water-organic media. On the basis of IR spectra, (1)H- and (13)C-NMR analysis the coordination mode of the ligand and most fitting structures of two isomeric complexes were proposed. The pharmacological investigations revealed that the new Pt(II) complex with 5-methyl-5-phenylhydantoin (PtMPH) as well as the previously described Pt(II) complexes with cyclopentanespiro-5'-hydantoin and cyclohexanespiro-5'-hydantoin (PtCHH) exerted concentration-dependent cytotoxic effect in a panel of human tumor cell lines. On the basis of the IC(50) values obtained PtMPH proved to be the most active cytotoxic agent. The other investigated complexes were less active, and among them PtCHH was the least potent antineoplastic agent. The pharmacodynamic investigation of PtMPH showed that this compound induces programmed cell death (apoptosis), as evidenced by the detection of oligonucleosomal DNA fragmentation in HL-60 cells after treatment with PtMPH.
authors.affiliation: Department of Chemistry, Medical University, 2 Dunav Street, 1000 Sofia, Bulgaria. georgi@satline.net
authors.forename: Adriana
authors.initials: A
authors.lastname: Bakalova
authors.forename: Rossen
authors.initials: R
authors.lastname: Buyukliev
authors.forename: Iovka
authors.initials: I
authors.lastname: Tcholakova
authors.forename: Georgi
authors.initials: G
authors.lastname: Momekov
authors.forename: Spiro
authors.initials: S
authors.lastname: Konstantinov
authors.forename: Margarita
authors.initials: M
authors.lastname: Karaivanova
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006827:Hydantoins / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D008024:Ligands; D046911:Macromolecular Substances; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity
chemical_list: C482656:5-methyl-5-phenylhydantoin Pt(II); D000970:Antineoplastic Agents; D006827:Hydantoins; D008024:Ligands; D046911:Macromolecular Substances; D009944:Organoplatinum Compounds; C107819:5-methyl-5-phenylhydantoin; D002945:Cisplatin