title: Synthesis, cytotoxicity, antibacterial and antitumor activity of platinum(II) complexes of 3-aminocyclohexanespiro-5-hydantoin.
abstract: New platinum(II) complexes of 3-aminocyclohexanespiro-5-hydantoin (achsh) were prepared and characterized. Ab initio calculation of the structure and the measurements of IR and NMR spectra of [Pt(NH(3))(achsh)Cl(2)] were also performed. Quantum-chemical and spectroscopic studies indicated a cis-square planar structure with a hydantoin ligand coordinated via the NH(2) group. The complexes were evaluated for in vitro cytotoxicity in murine erythroleukemia (MEL) cells, clone F4N, as well as for in vivo antitumor activity toward murine L1210 leukemia. The complexes exerted significantly lower in vitro and in vivo toxicities compared with those of cisplatin (cis-diamminedichloroplatinum(II), DDP). The complex [Pt(NH(3))(achsh)Cl(2)] exhibited antitumor activity against L1210 leukemia, comparable to that of cisplatin, resulting at a dose of 72 mg/kg in a %T/C (increased survival time) of 191%. This complex, as well as cisplatin, induced apoptosis in F4N cells, and exerted antibacterial activity as assessed in 10 bacterial strains.
authors.affiliation: Institute of Molecular Biology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str. bl. 21, BG-1113 Sofia, Bulgaria.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kushev
authors.forename: Galina
authors.initials: G
authors.lastname: Gorneva
authors.forename: Venelin
authors.initials: V
authors.lastname: Enchev
authors.forename: Emilya
authors.initials: E
authors.lastname: Naydenova
authors.forename: Julita
authors.initials: J
authors.lastname: Popova
authors.forename: Svetoslav
authors.initials: S
authors.lastname: Taxirov
authors.forename: Liliana
authors.initials: L
authors.lastname: Maneva
authors.forename: Konstantin
authors.initials: K
authors.lastname: Grancharov
authors.forename: Nadejda
authors.initials: N
authors.lastname: Spassovska
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D001419:Bacteria / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D006827:Hydantoins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D009368:Neoplasm Transplantation; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000633:toxicity; D017671:Platinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D013055:Spectrophotometry, Infrared; D014407:Tumor Cells, Cultured
chemical_list: C460960:(Pt(NH(3))(achsh)Cl(2)); D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D006827:Hydantoins; D009944:Organoplatinum Compounds; D017671:Platinum Compounds