A series of novel 3-amino-1,2,4-benzotriazine-1,4-dioxide derivatives were synthesized and screened for their in vitro cytotoxicity against promyelocytic leukemia HL-60, androgen-independent prostate tumor PC3, hepatocellular carcinoma Bel-7402, human esophagus tumor ECA-109, and human breast tumor MCF-7 cell lines in hypoxia and in normoxia. Most compounds showed higher cytotoxic activity both in hypoxia and in normoxia. Among them, compounds 61 and 62 showed more potent cytotoxic activity and hypoxic selectivity when compared to tirapazamine.
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