2-Arylidene-4-cyclopentene-1,3-diones designed as non-nitro radiosensitizers and hypoxic cytotoxins.
The radiosensitizing effects and hypoxic cytotoxicity of 2-(4'-hydroxybenzylidene)-cyclopentene-1,3-dione (KIH-200) and its 3'-methoxy and 3',5'-dimethoxy derivatives (KIH-201 and KIH-202) were investigated in vitro. These synthetic compounds were newly designed as non-nitro electron-affinic radiosensitizers and hypoxic cytotoxins on the basis of their high electron affinities and electrostatic potentials which were estimated by semiempirical molecular orbital calculation using the CNDO/2 program. The compounds were shown to have weak but apparent hypoxic cytotoxicity to FM3A cells from C3H mice. On irradiation in the presence of KIH-201 or KIH-202, hypoxic cells were more sensitive than aerobic cells at very low drug concentrations (below 10 microM), whereas KIH-200 was less effective.
D000818:Animals; D001597:Benzylidene Compounds; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003603:Cytotoxins; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D000860:Hypoxia; D051379:Mice; D011838:Radiation-Sensitizing Agents; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects
D001597:Benzylidene Compounds; D003603:Cytotoxins; D011838:Radiation-Sensitizing Agents; C054270:2-(3'-methoxy-4'-hydroxybenzylidene)cyclopentene-1,3-dione; C054272:KIH 202