2. Academic Validation
  3. Synthesis and hypoxic-cytotoxic activity of some 3-amino-1,2,4-benzotriazine-1,4-dioxide derivatives

Synthesis and hypoxic-cytotoxic activity of some 3-amino-1,2,4-benzotriazine-1,4-dioxide derivatives

  • Bioorg Med Chem Lett. 2006 Aug 15;16(16):4209-13. doi: 10.1016/j.bmcl.2006.05.095.
Faqin Jiang 1,  Bo Yang,  Lingling Fan,  Qiaojun He,  Yongzhou Hu
Affiliations

Affiliation

  • 1 ZJU-ENS Joint Laboratory of Medicinal Chemistry, School of Pharmaceutical Sciences, Zhejiang University, Hubin campus, Hangzhou, China.
PMID: 16777409 DOI: 10.1016/j.bmcl.2006.05.095
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)).

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