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 μM), whereas KIH-200 was less effective. (author)