title: Synthesis and hypoxic-cytotoxic activity of some 3-amino-1,2,4-benzotriazine-1,4-dioxide derivatives.
abstract: A series of 3-amino-1,2,4-benzotriazine-1,4-dioxide derivatives 1 have been synthesized and evaluated for their cytotoxic activity in vitro against human leukemia cell lines: Molt-4, K562, HL60, human liver cancer cell Hep-G2, human prostate cancer cell PC-3 in hypoxia. Most of the compounds showed more potent activity than TPZ. Compounds 1i and 1m displayed encouraging superior activity against Molt-4 and HL-60 cell lines. Three potential derivatives received the test of the activity in hypoxia and in normoxia against Molt-4 and HL-60 cell lines and showed obvious hypoxia selectivity. Further mechanism study revealed that the cytotoxic activities of compounds 1i and 1k in Molt-4 cells might be mediated by modulation of p53 protein expression and mitochondrial membrane potential (DeltaPsi(m)).
authors.affiliation: ZJU-ENS Joint Laboratory of Medicinal Chemistry, School of Pharmaceutical Sciences, Zhejiang University, Hubin campus, Hangzhou, China.
authors.forename: Faqin
authors.initials: F
authors.lastname: Jiang
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Lingling
authors.initials: L
authors.lastname: Fan
authors.forename: Qiaojun
authors.initials: Q
authors.lastname: He
authors.forename: Yongzhou
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D000860:Hypoxia; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D008564:Membrane Potentials; D008956:Models, Chemical; D000077704:Tirapazamine; D014227:Triazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D014227:Triazines; D016159:Tumor Suppressor Protein p53; D000077704:Tirapazamine