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: Faqin Jiang, Bo Yang, Lingling Fan, Qiaojun He, Yongzhou Hu
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 16 Issue 16 Pg. 4209-13 (Aug 15 2006) ISSN: 0960-894X [Print] England
• PMID: 16777409 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Triazines
• Tumor Suppressor Protein p53
• Tirapazamine

Topics

• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• Drug Screening Assays, Antitumor
• HL-60 Cells
• Humans
• Hypoxia
• Inhibitory Concentration 50
• K562 Cells
• Membrane Potentials
• Models, Chemical
• Tirapazamine
• Triazines (chemical synthesis, chemistry, pharmacology)
• Tumor Suppressor Protein p53 (metabolism)