Spin-label substitutions in cisplatin reduce toxicity and interaction with radiation.
A piperidinyl-labeled platinum(II) complex, cis-Pt[2,2,6,6-tetramethyl-4-aminopiperidine-N-oxyl]2dichloride , is an ESR-traceable analog of the antitumor agent, cis-diamminedichloroplatinum(II), DDP. The toxicity of the analog (PDN-1) in Chinese hamster ovary (CHO) cells is 22 times less than that of the parent compound: D0 (where D0 = slope-1 of the straight-line portion of the survival curve) = 0.11 mM versus 0.0053 mM for 1.5-h treatments with PDN-1 and DDP, respectively. At PDN-1 doses that cause 10% killing when used alone, no statistically significant increase in cell killing of hypoxic, irradiated cells was observed. PDN-1 does not have significant dose-modifying properties but may be a useful probe to study platinum in mammalian cells.
D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D002478:Cells, Cultured; D002945:Cisplatin / Q000031:analogs & derivatives* / Q000633:toxicity; D006224:Cricetinae; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D005347:Fibroblasts; D066298:In Vitro Techniques; D011829:Radiation Dosage; D011838:Radiation-Sensitizing Agents; D013113:Spin Labels; D013329:Structure-Activity Relationship
D011838:Radiation-Sensitizing Agents; D013113:Spin Labels; C048391:PDN-1; D002945:Cisplatin