Effect of arylidene-cyclopentenedione radiosensitizers on ATP synthesis in mitochondria: action as potent inhibitors of phosphate transport.
The effects of the arylidene-cyclopentenedione radiosensitizers, KIH-200, 201 and 202 on ATP synthesis in mitochondria were examined. In spite of the close similarity of their chemical structure to that of the most potent known weakly acidic uncoupler, SF 6847, they did not show any uncoupling activity at concentrations of up to 50 microM. However, these three compounds were found to have very potent inhibitory effects on Pi-transport into mitochondria, all causing 50% inhibition (I50%) at about 7 microM. Thus they are much more potent than the commonly used Pi-transport inhibitors N-ethylmaleimide (I50% = about 40 microM), and mersalyl (I50% = about 30 microM). They may act as SH-reagents, and inhibit Pi-transport by modifying an SH-group(s) in the Pi-transporter.
Koike
H
H
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
Hori
H
H
Inayama
S
S
Terada
H
H
D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D001597:Benzylidene Compounds / Q000494:pharmacology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D005033:Ethylmaleimide / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D028044:Phosphate-Binding Proteins; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D001597:Benzylidene Compounds; D002352:Carrier Proteins; D009570:Nitriles; D028044:Phosphate-Binding Proteins; D011838:Radiation-Sensitizing Agents; C001784:SF 6847; C054269:2-(4'-hydroxybenzylidene)cyclopentene-1,3-dione; C054272:KIH 202; D000255:Adenosine Triphosphate; D005033:Ethylmaleimide