A new class of dual-function nitroazole derivatives that are composed of electron-affinic nitroazole rings and a thiol-reactive alpha, beta-unsaturated carbonyl side chain were synthesized to evaluate their physico-chemical properties, reactivity with glutathione (GSH), and cytotoxicity and radiosensitizing activity towards EMT6/KU cells in vitro. Among this class of nitroazole compounds, 2-nitroimidazole-derivative (1), 3-nitro-1,2,4-triazole derivative (2), and 2-methyl-4-nitroimidazole derivative (3) with a common side-chain structure of trans CH2CH = CHCO2CH3 readily reacted with GSH in phosphate-buffer solution (pH 7.2, 310 K). These compounds showed higher cytotoxicities to both aerobic and hypoxic EMT6/KU cells than the corresponding alpha, beta-saturated counterparts (6-8) with a side-chain structure of CH2CH2CH2CO2CH2CH3. The hypoxic cytotoxicity of 1 and 2 with similar electron affinities to that of misonidazole (9) was potentiated by the combined effects of depletion of non-protein thiols (NPSH) by the alpha, beta-unsaturated carbonyl side chains and bioreduction of the nitroazole rings. The sensitizer enhancement ratios in vitro (SERvitro) of 1 (2.80 +/- 0.20) and 2 (2.63 +/- 0.27) at a dose of 1.0 mmol dm-3 are comparable with the oxygen enhancement ratio (OER = 2.90 +/- 0.10) and are significantly larger than those of their respective counterparts 6 (1.28 +/- 0.06) and 7 (1.22 +/- 0.09). A less electron-affinic compound, 3, also gave a large SERvitro = 1.80 +/- 0.18, whereas the counterpart 8 was not effective (1.10) in radiosensitizing hypoxic cells. Compounds 1-3 not only altered the slope, but also reduced the shoulder of the dose-survival curve. These 'dual-function' nitroazole radiosensitizers show much lower levels of in vitro radiosensitization, as measured by the C1-6, than the previously reported 'anomalous' radiosensitizers such as 5-substituted 4-nitroimidazole radiosensitizers.