Synthesis, hypoxia-selective cytotoxicity of new 3-amino-1,2,4-benzotriazine-1,4-dioxide derivatives

  • Eur J Med Chem. 2011 Mar;46(3):919-26. doi: 10.1016/j.ejmech.2011.01.007.
Qing Xia  1 ,  Ling Zhang ,  Jun Zhang ,  Rong Sheng ,  Bo Yang ,  Qiaojun He ,  Yongzhou Hu
Affiliations
  • 1. ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Zijingang Campus, Hangzhou 310058, China.
PMID: 21281992 DOI: 10.1016/j.ejmech.2011.01.007
Abstract

We reported the synthesis, hypoxic cytotoxic activities and selectivities of 18 new 3-(alkoxymethylamino)-1,2,4-benzotriazine 1,4-dioxides. The synthesized compounds were screened in vitro against 5 cell lines: K562, SMMC-7721, A549, PC-3 and KB in hypoxia and in normoxia. Some of them showed higher or similar cytotoxic activity when compared to tirapazamine. Physico-chemical study showed the positive correlation between hypoxic activity and lipophilicity within a certain range. Preliminary mechanism study on the potent derivatives 4b, 4l and 4m indicated that the cytotoxic activities of these compounds might be mediated by inducing Apoptosis.