Synthesis, physicochemical and in vitro pharmacological investigation of new platinum (II) complexes with some cycloalkanespiro-5'-hydantoins.
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.
Bakalova
Adriana
A
Department of Chemistry, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Street, 1000 Sofia, Bulgaria.
Buyukliev
Rossen
R
Momekov
Georgi
G
Ivanov
Darvin
D
Todorov
Dimitar
D
Konstantinov
Spiro
S
Karaivanova
Margarita
M
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
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