Synthesis and antitumor activity of platinum(II) complexes with trans-3,4-diamino-2,2,6,6-tetramethylpiperidine-1-oxyl.
Platinum complexes PtII(DAPO)X2 with diaminonitroxyl radical-trans-3,4-diamino-2,2,6,6-tetramethylpiperidine-1-oxyl (DAPO)-were synthesized by the direct reaction of DAPO with K2PtX4 (X = Cl, I) or by the replacement of chloro ligands in PtII(DAPO)Cl2 by bromo, nitrato, oxalato, malonato, and 1,1-cyclobutanedicarboxylato ligands. The complexes thus obtained were characterized by elemental analysis, infrared,electronic, electron paramagnetic resonance spectroscopic techniques, and high-performance liquid chromatography. The toxicity of compounds in terms of LD50 strongly depends on the nature of X-ligands, and varies between 11 mg/kg (X = NO3) and 400 mg/kg (X2 = 1,1-cyclobutanedicarboxylate). Up to 66% of mice bearing leukemia L1210 survive after the administration of these complexes. This effect is comparable to the effect of cisplatin (50% survive). An increase in the life span of the rest of the animals ranges from 158 to 383%. Complex PtII(DAPO)Cl2 appears to be more efficient than cisplatin against adenocarcinoma 755. Cisplatin, cis-diamminedichloroplatinum(II); CBDCA, 1,1-cyclobutanedicarboxylic acid; DAPO, trans-3,4-diamino-2,2,6,6-tetramethylpiperidine-1-oxyl; Mal, malonic acid; Ox, oxalic acid; IR, infrared; EPR, electron paramagnetic resonance; HPLC, high-performance liquid chromatography; Ca755, adenocarcinoma 755; LD50 and LD100, dose of compounds (mg/kg), causing a death of 50 or 100% or treated animals; ILS, increase in life span of mice.
Sen'
V D
VD
Institute of Chemical Physics, Chernogolovka, Russian Academy of Sciences, Moscow Region, Russia.
Golubev
V A
VA
Volkova
L M
LM
Konovalova
N P
NP
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D005260:Female; D007928:Lethal Dose 50; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds