21725-69-9Relevant articles and documents
Identification of a bacteria-produced benzisoxazole with antibiotic activity against multi-drug resistant Acinetobacter baumannii
Deering, Robert W.,Whalen, Kristen E.,Alvarez, Ivan,Daffinee, Kathryn,Beganovic, Maya,LaPlante, Kerry L.,Kishore, Shreya,Zhao, Sijing,Cezairliyan, Brent,Yu, Shen,Rosario, Margaret,Mincer, Tracy J.,Rowley, David C.
, p. 370 - 380 (2021/02/22)
The emergence of multi-drug resistant pathogenic bacteria represents a serious and growing threat to national healthcare systems. Most pressing is an immediate need for the development of novel antibacterial agents to treat Gram-negative multi-drug resistant infections, including the opportunistic, hospital-derived pathogen, Acinetobacter baumannii. Herein we report a naturally occurring 1,2-benzisoxazole with minimum inhibitory concentrations as low as 6.25 μg ml?1 against clinical strains of multi-drug resistant A. baumannii and investigate its possible mechanisms of action. This molecule represents a new chemotype for antibacterial agents against A. baumannii and is easily accessed in two steps via de novo synthesis. In vitro testing of structural analogs suggest that the natural compound may already be optimized for activity against this pathogen. Our results demonstrate that supplementation of 4-hydroxybenzoate in minimal media was able to reverse 1,2-benzisoxazole’s antibacterial effects in A. baumannii. A search of metabolic pathways involving 4-hydroxybenzoate coupled with molecular modeling studies implicates two enzymes, chorismate pyruvate-lyase and 4-hydroxybenzoate octaprenyltransferase, as promising leads for the target of 3,6-dihydroxy-1,2-benzisoxazole.
Preparation method of 1,2-benzisothiazole-3-ketone
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Paragraph 0014; 0015; 0016, (2016/11/14)
The invention provides a preparation method of 1,2-benzisothiazole-3-ketone. The preparation method comprises the following steps of dissolving salicylhydroxamic acid into methanol; adding sodium hypochlorite with the concentration being 10 to 20 percent; taking a reaction for 20 to 40s at room temperature; performing dilution by distilled water; performing extraction by ethyl acetate; performing organic phase drying by distillation to obtain slight yellow solid; performing suction filtration to obtain a product of the 1,2-benzisothiazole-3-ketone. The method has the advantages that the synthesis process is simple; the cost is low; green and environment-friendly effects are achieved; the time is short; no byproduct is produced; the yield is as high as more than 82 percent.
Inhibition of thioredoxin reductase by a novel series of bis-1,2-benzisoselenazol-3(2H)-ones: Organoselenium compounds for cancer therapy
He, Jie,Li, Dongdong,Xiong, Kun,Ge, Yongjie,Jin, Hongwei,Zhang, Guozhou,Hong, Mengshi,Tian, Yongliang,Yin, Jin,Zeng, Huihui
, p. 3816 - 3827 (2012/08/27)
Thioredoxin reductase (TrxR) is critical for cellular redox regulation and is involved in tumor proliferation, apoptosis and metastasis. Its C-terminal redox-active center contains a cysteine (Cys497) and a unique selenocysteine (Sec498), which are exposed to solvent and easily accessible. Thus, it is becoming an important target for anticancer drugs. Selective inhibition of TrxR by 1,2-(bis-1,2-benzisoselenazol-3(2H)-one)ethane (4a) prevents proliferation of several cancer cell lines both in vivo and in vitro. Using the structure of 4a as a starting point, a series of novel bis-1,2-benzisoselenazol-3(2H)-ones was designed, prepared and tested to explore the structure-activity relationships (SARs) for this class of inhibitor and to improve their potency. Notably, 1,2-(5,5′-dimethoxybis(1,2-benzisoselenazol-3(2H)-one))ethane (12) was found to be more potent than 4a in both in vitro and in vivo evaluation. Its binding sites were confirmed by biotin-conjugated iodoacetamide assay and a SAR model was generated to guide further structural modification.
