36389-16-9Relevant academic research and scientific papers
Discovery of novel nitrogenous heterocyclic-containing quinoxaline-1,4-di-N-oxides as potent activator of autophagy in M.tb-infected macrophages
Zhang, Heying,Lu, Qirong,Zhang, Jie,Qu, Wei,Xie, Shuyu,Huang, Lingli,Yuan, Zonghui,Pan, Yuanhu
, (2021/07/06)
As a continuation of our research on antimycobacterial agents, a series of novel quinoxaline-1,4-di-N-oxides (QdNOs) containing various nitrogenous heterocyclic moieties at the R6 position were designed and synthesized. Antimycobacterial activities, as well as the cytotoxic effects, of the compounds were assayed. Four compounds (6b, 6f, 6n, and 6o), characterized by 2-carboxylate ethyl or benzyl ester, 6-imidazolyl or 1,2,4-triazolyl, and a 7-fluorine group, exhibited the most potent antimycobacterial activity against M.tb strain H37Rv (MIC ≤ 0.25 μg/mL) with low toxicity in VERO cells (SI = 169.3–412.1). Compound 6o also exhibited excellent antimycobacterial activity in an M.tb-infected macrophage model and was selected for further exploration of the mode of antimycobacterial action of QdNOs. The results showed that compound 6o was capable of disrupting membrane integrity and disturbing energy homeostasis in M.tb. Furthermore, compound 6o noticeably increased cellular ROS levels and, subsequently, induced autophagy in M.tb-infected macrophages, possibly indicating the pathways of QdNOs-mediated inhibition of intracellular M.tb replication. The in vivo pharmacokinetic (PK) profiles indicated that compounds 6o was acceptably safe and possesses favorable PK properties. Altogether, these findings suggest that compound 6o is a promising antimycobacterial candidate for further research.
Cu-Catalyzed π-Core Evolution of Benzoxadiazoles with Diaryliodonium Salts for Regioselective Synthesis of Phenazine Scaffolds
Sheng, Jinyu,He, Ru,Xue, Jie,Wu, Chao,Qiao, Juan,Chen, Chao
supporting information, p. 4458 - 4461 (2018/08/09)
The Cu-catalyzed regioselective synthesis of phenazine N-oxides was realized from benzoxadiazoles and diaryliodonium salts. The process was initiated by the electrophilic arylation of benzoxadiazoles with diaryliodonium salts and followed by benzocyclization reactions. The further reduction of N-oxides in situ to phenazine scaffolds and deviation to organic fluorescent materials were readily accomplished.
Synthesis of novel fluorobenzofuroxans by oxidation of anilines and thermal cyclization of arylazides
Leyva, Socorro,Castanedo, Víctor,Leyva, Elisa
, p. 171 - 175 (2007/10/03)
The synthesis of several fluorobenzofuroxans by oxidation of fluoroanilines and thermal cyclization of fluoroarylazides is presented. The fluorobenzofuroxans prepared in this study presented tautomerism as evidenced by their NMR data. Benzofuroxans in general have biological activity and are synthetic intermediates for the preparation of several compounds with important pharmaceutical applications.
Hypoxia-Selective Agents Derived from Quinoxaline 1,4-Di-N-oxides
Monge, Antonio,Palop, Juan A.,Cerain, Adela Lopez de,Senador, Virginia,Martinez-Crespo, Francisko J.,et al.
, p. 1786 - 1792 (2007/10/02)
Hypoxic cells, which are a common feature of solid tumors, but not normal tissues, are resistant to both anticancer drugs and radiation therapy.Thus the identification of drugs with selective toxicity toward hypoxic cells is an important objective in anticancer chemotherapy.The benzotriazine di-N-oxide (SR 4233, Tirapazamine) has been shown to be an efficient and selective cytotoxin for hypoxic cells.Since the bioreductive activation of Tirapazamine is thought to be due to the presence of the 1,4-di-N-oxide moiety, a series of 3-aminoquinoxaline-2-carbonitrile 1,4-di-N-oxides with a range of electron-donating and -withdrawing substituents in the 6- and /or 7- positions has been synthesized and evaluated for toxicity to hypoxic cells.Electrochemical studies of the quinoxaline di-N-oxides and Tirapazamine showed that as the electron-withdrawing nature of the 6(7)-substituent increases, the reduction potential becomes more positive and the compound is more readily reduced.Apart from the unsubstituted 6a and the 6,7-dimethyl derivative 6c, the quinoxaline di-N-oxide have reduction potentials significantly more positive than Tirapazamine (Epc -0.90 V).The most potent cytotoxins to cells in culture were the 6,7-dichloro and 6,7-difluoro derivatives 6i and 6l, which were 30-fold more potent than Tirapazamine.The 6(7)-fluoro and 6(7)-chloro compounds, 6e and 6h, showed the greatest hypoxia selectivity.Four of the compounds, 6e, 6f, 6h and 6i, killed the inner cells of multicellular tumor spheroids in vitro.In vivo Balb/c mice tolerated a dose of these four compounds twice the size of that of Tirapazamine.This study demonstrates that quinoxaline 1,4-di-N-oxides could provide useful hypoxia-selective therapeutic agents.
