title: Platinum(IV) complexes with some derivatives of 5-methyl-5-(4-pyridyl) hydantoin. Synthesis, study and comparative pharmacological investigation.
abstract: 3 Pt(IV) complexes with 3-ethyl-5-methyl-5-(4-pyridyl)hydantoin (4), 3-propyl-5-methyl-5-(4-pyridyl)hydantoin (5) and 3-benzyl-5-methyl-5-(4-pyridyl)hydantoin (6) with general formulae cis-[Pt(L)2Cl4] were synthesized. The novel compounds were characterized by elemental analysis, IR, 1H, 13C, NMR spectra in solid state and in solution. The studies showed that the ligands coordinate to the platinum ions in a monodentate manner through the nitrogen atom from the pyridine ring. The cytotoxic activity in vitro of newly synthesized complexes as well as their previously prepared analogous of Pt(IV) with other derivatives like 3-amino-5-methyl-5-(4-pyridyl)hydantoin (1), 5-methyl-5-(4-pyridyl)hydantoin (2), 3,5-dimethyl-5-(4-pyridyl)hydantoin (3) was screened against a panel of human tumor cell lines. The tested compounds displayed cytotoxic activity which was invariably superior with the Pt(IV) complex with 3-benzyl-5-methyl-5-(4-pyridyl)hydantoin (6) causing 50% inhibition of cellular viability at micromolar concentration, though the activity of the other studied Pt(IV) complexes proved to greatly decrease in the order 5-4-3-2-1.
authors.affiliation: Department of Chemistry, Faculty of Pharmacy, Medical University of Sofia, Sofia, Bulgaria.
authors.forename: A
authors.initials: A
authors.lastname: Bakalova
authors.forename: R
authors.initials: R
authors.lastname: Buyukliev
authors.forename: Z
authors.initials: Z
authors.lastname: Ivanova
authors.forename: G
authors.initials: G
authors.lastname: Momekov
authors.forename: D
authors.initials: D
authors.lastname: Ivanov
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D006801:Humans; D006827:Hydantoins / Q000138:chemical synthesis* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D006827:Hydantoins; D009944:Organoplatinum Compounds