Propargylic sulfones possessing a 2-nitroimidazole function: novel hypoxic-cell radiosensitizers with intracellular non-protein thiol depletion ability

Hypoxia-selective activation of 5-fluorodeoxyuridine prodrug possessing indolequinone structure: radiolytic reduction and cytotoxicity characteristics

“…[1][2][3][4][5] Hypoxic cells have been recognized to show resistance to ionizing radiation, the biological action of which involves acceleration of oxidation, thus leading to post-irradiation regrowth of tumor. 6 For the radiation therapy of hypoxic tumor cells, there have been various strategies including hyperbaric oxygen therapy, 7,8 hypoxic cell radiosensitizers, [9][10][11][12] and hypoxic cytotoxins. 13 A new strategy to overcome tumor hypoxia focuses on the combination of radiotherapy and chemotherapy into prodrugs that are activated to release antitumor agents by hypoxic irradiation.…”

Current molecular design of intelligent drugs and imaging probes targeting tumor-specific microenvironments

“…41 It is therefore likely that depletion of GSH in tumor cells is an effective target for radiation therapy. We have proposed a series of nitroazole radiosensitizers containing an a,b-unsaturated carbonyl group ( 22) 42 or propargylic sulfones ( 23) 43 in the side chains, which are able to capture GSH in tumor cells by alkylation (Fig. 6).…”

Synthesis of the enantiomers of the dual function 2‐nitroimidazole radiation sensitizer RB 6145

“…These include metronidazole [3], misonidazole [4] (Fig. 1), and more recently bifunctional 2-nitroimidazole derivatives, possessing alkylating functionality, capable of anti-angiogenic activity [5] or depletion of endogenous non-protein thiols (NPSH) such as reduced glutathione [6]. These effects have been found to play a crucial function in determining the response of cells to several types of radiation.…”