Substituted azole diones (II) and (III) are provided that kill cells, suppress cell proliferation, suppress cell growth, abrogate the cell cycle G2 checkpoint and/or cause adaptation to G2 cell cycle arrest. Methods of making the invention compounds are provided. The invention provides substituted azole diones (II) and (III) to treat cell proliferation disorders. The invention includes the substituted azole diones (II) and (III) for use to selectively kill or suppress cancer cells without additional anti-cancer treatment. The invention includes the cell cycle G2- checkpoint-abrogating substituted azole diones (II) and (III) for use to selectively sensitize cancer cells to DNA damaging reagents, treatments and/or other types of anti-cancer reagents.