921933-23-5Relevant academic research and scientific papers
Discovery and optimization of benzotriazine Di-N-oxides targeting replicating and nonreplicating mycobacterium tuberculosis
Chopra, Sidharth,Koolpe, Gary A.,Tambo-Ong, Arlyn A.,Matsuyama, Karen N.,Ryan, Kenneth J.,Tran, Tran B.,Doppalapudi, Rupa S.,Riccio, Edward S.,Iyer, Lalitha V.,Green, Carol E.,Wan, Baojie,Franzblau, Scott G.,Madrid, Peter B.
experimental part, p. 6047 - 6060 (2012/09/05)
Compounds bactericidal against both replicating and nonreplicating Mtb may shorten the length of TB treatment regimens by eliminating infections more rapidly. Screening of a panel of antimicrobial and anticancer drug classes that are bioreduced into cytotoxic species revealed that 1,2,4-benzotriazine di-N-oxides (BTOs) are potently bactericidal against replicating and nonreplicating Mtb. Medicinal chemistry optimization, guided by semiempirical molecular orbital calculations, identified a new lead compound (20q) from this series with an MIC of 0.31 μg/mL against H37Rv and a cytotoxicity (CC 50) against Vero cells of 25 μg/mL. 20q also had equivalent potency against a panel of single-drug resistant strains of Mtb and remarkably selective activity for Mtb over a panel of other pathogenic bacterial strains. 20q was also negative in a L5178Y MOLY assay, indicating low potential for genetic toxicity. These data along with measurements of the physiochemical properties and pharmacokinetic profile demonstrate that BTOs have the potential to be developed into a new class of antitubercular drugs.
Synthesis, structure and hypoxic cytotoxicity of 3-amino-1,2,4- benzotriazine-1,4-dioxide derivatives
Jiang, Faqin,Weng, Qinjie,Sheng, Rong,Xia, Qing,He, Qiaojun,Yang, Bo,Hu, Yongzhou
, p. 258 - 263 (2008/02/09)
A series of novel 3-amino-1,2,4-benzotriazine-1,4-dioxide derivatives were synthesized and screened for their in vitro cytotoxicity against promyelocyte leukemia HL-60, androgen-independent prostate tumor PC3, hepatocellular carcinoma Bel-7402, human esop
Synthesis and hypoxic-cytotoxic activity of some 3-amino-1,2,4-benzotriazine-1,4-dioxide derivatives
Jiang, Faqin,Yang, Bo,Fan, Lingling,He, Qiaojun,Hu, Yongzhou
, p. 4209 - 4213 (2007/10/03)
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 (ΔΨm).
