One-electron reduction of 2- and 6-methyl-1,4-naphthoquinone bioreductive alkylating agents

Journal Article · Fri Aug 01 04:00:00 EDT 1986 · J. Med. Chem.; (United States)

DOI:https://doi.org/10.1021/jm00158a010· OSTI ID:5035222

Wilson, I; Wardman, P; Lin, T S; Sartorelli, A C

The semiquinones, Q.-, of derivatives of 2- and 6-methyl-1,4-naphthoquinones, some incorporating leaving groups with substituents such as CH/sub 2/Br or CH/sub 2/OCONHCH/sub 3/, have been produced by radiolytic reduction of Q by (CH/sub 3/)2COH radicals. The absorption spectra and decay kinetics of Q.- were all closely similar to that produced from 2-methyl-1,4-naphthoquinone, with no evidence for unimolecular elimination of a leaving group in the semiquinone form, but immediate loss of leaving group upon two-electron reduction of Q to the hydroquinone. The redox equilibria between Q/Q.- and O2/O2.- were characterized, and reduction potentials of the couples Q/Q.- in water at pH 7.6 were calculated. The implications of these observations for the use of these compounds as bioreductive alkylating agents or as radiosensitizers with potential selective activity toward hypoxic cells are discussed.

• Research Organization: Gray Laboratory of the Cancer Research Campaign, Middlesex, England
• OSTI ID: 5035222
• Journal Information: J. Med. Chem.; (United States), Journal Name: J. Med. Chem.; (United States) Vol. 8; ISSN JMCMA
• Country of Publication: United States
• Language: English

Related Subjects

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY
400600* -- Radiation Chemistry
ABSORPTION SPECTRA
ALKYLATING AGENTS
AROMATICS
CHEMICAL RADIATION EFFECTS
CHEMICAL REACTIONS
CHEMISTRY
DECOMPOSITION
DRUGS
ELECTRONS
ELEMENTARY PARTICLES
FERMIONS
LEPTONS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
QUINONES
RADIATION CHEMISTRY
RADIATION EFFECTS
RADIOLYSIS
RADIOSENSITIZERS
REDUCTION
SPECTRA
USES