Charge transfer-oxy radical mechanism for anti-cancer agents.
The proposal is advanced that anti-cancer drugs generally function by charge transfer resulting in formation of toxic oxy radicals which destroy the neoplasm. Electrochemical studies were performed with some of the main types of agents: iminium ions (adenine iminium from alkylating species, iminium metabolite of 6-mercaptopurine, nitidine, other polynuclear iminiums) and metal complexes (Pt(II)diaquodiammine-guanosine, copper salicylaldoximes). Reduction potentials ranged from -0.4 to -1.2 V. Literature data for quinones are presented and radiation is discussed. Based on the theoretical framework, a rationale is offered for the carcinogen-anti-cancer paradox and the role of antioxidants.
Kovacic
P
P
Department of Chemistry, University of Wisconsin-Milwaukee 53201.
Ames
J R
JR
Lumme
P
P
Elo
H
H
Cox
O
O
Jackson
H
H
Rivera
L A
LA
Ramirez
L
L
Ryan
M D
MD
D000478:Alkylation; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants; D004247:DNA / Q000378:metabolism; D004611:Ellipticines / Q000494:pharmacology; D005609:Free Radicals; D015122:Mercaptopurine / Q000494:pharmacology; D008670:Metals / Q000494:pharmacology; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy; D010100:Oxygen / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology; D011809:Quinones / Q000494:pharmacology
D000970:Antineoplastic Agents; D000975:Antioxidants; D004611:Ellipticines; D005609:Free Radicals; D008670:Metals; D011804:Quinolines; D011809:Quinones; C034192:ellipticine; D004247:DNA; D015122:Mercaptopurine; D010100:Oxygen