Synthesis, cytotoxicity, antibacterial and antitumor activity of platinum(II) complexes of 3-aminocyclohexanespiro-5-hydantoin.
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.
Kushev
Daniel
D
Institute of Molecular Biology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str. bl. 21, BG-1113 Sofia, Bulgaria.
Gorneva
Galina
G
Enchev
Venelin
V
Naydenova
Emilya
E
Popova
Julita
J
Taxirov
Svetoslav
S
Maneva
Liliana
L
Grancharov
Konstantin
K
Spassovska
Nadejda
N
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
C460960:(Pt(NH(3))(achsh)Cl(2)); D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D006827:Hydantoins; D009944:Organoplatinum Compounds; D017671:Platinum Compounds