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

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.

• Authors: Qing Xia, Ling Zhang, Jun Zhang, Rong Sheng, Bo Yang, Qiaojun He, Yongzhou Hu
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 46 Issue 3 Pg. 919-26 (Mar 2011) ISSN: 1768-3254 [Electronic] France
• PMID: 21281992 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents
• Triazines
• Tirapazamine

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Hypoxia (drug effects)
• Cell Line, Tumor
• Drug Screening Assays, Antitumor
• Humans
• Neoplasms (drug therapy)
• Structure-Activity Relationship
• Tirapazamine
• Triazines (chemical synthesis, chemistry, pharmacology)