1381782-02-0Relevant articles and documents
Synthesis and evaluation of 8-hydroxyquinolin derivatives substituted with (benzo[d][1,2]selenazol-3(2H)-one) as effective inhibitor of metal-induced Aβ aggregation and antioxidant
Wang, Bo,Wang, Zhiren,Chen, Hong,Lu, Chuan-Jun,Li, Xingshu
, p. 4741 - 4749 (2016)
A series of 8-hydroxyquinolin derivatives substituted with (benzo[d][1,2]selenazol-3(2H)-one) at the 2-position were synthesized and evaluated for treatment of Alzheimer's disease. In vitro assays demonstrated that most of the target compounds exhibit significant inhibition of Cu(II)-induced Aβ1–42aggregation, rapid H2O2scavenging and glutathione peroxidise (GPx)-like catalytic activity. Among these molecules, compound 9a is the most potent peroxide scavenger that possesses the ability to scavenge most H2O2within 200–220 min and possesses GPx-like activity (v0= 106.0 μM·min?1), enabling modulation of metal-induced Aβ aggregation.
Pyrimidine-selenium benzoic acid derivative as well as preparation method and application thereof as herbicide
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Paragraph 0066-0067, (2021/11/19)
The invention belongs to the technical field of herbicides, and particularly relates to a pyrimidine-selenium benzoic acid derivative as well as a preparation method and application thereof as a herbicide. The compound is subjected to nucleophilic substit
Synthesis and antiproliferative evaluation of novel steroid-benzisoselenazolone hybrids
Cui, Jianguo,Wei, Meizhen,Pang, Liping,Gan, Chunfang,Xiao, Junan,Shi, Haixin,Zhan, Junyan,Liu, Zhiping,Huang, Yanmin
, (2019/10/04)
The two different types of steroidal benzisoselenazolone hybrids were synthesized by incorporating benzisoselenazolone scaffold into dehydroepiandrosterone and B-norcholesterol. The antiproliferative activity of the synthesized compounds against some carcinoma cell lines were investigated. The results showed that some of these compounds have better inhibitory activity than abiraterone on the proliferation of tumor cells associated with human growth hormone, and have less cytotoxicity on normal human cells. In particular, the IC50 values of the compound 8a and 8f are 5.4 and 6.5 μmol/L against human ovarian carcinoma (SKOV3) cell line, and possess SI values of 13.9 and 10.5, respectively. The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs.
Benzisoselenazolone quinoline derivative and application thereof in treatment of Alzheimer's disease
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Paragraph 0049; 0050; 0051; 0052; 0053; 0054, (2017/08/25)
The invention provides a benzisoselenazolone quinoline derivative as shown in a formula I, or pharmaceutically acceptable salts, hydrate, solvates, crystal-form isomers or diastereoisomers thereof, as well as an application of compounds or compositions in
Synthesis and applications of benzisoselenazolone modified nitrosourea compound
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Paragraph 0082; 0083; 0084; 0085; 0086; 0087; 0088;0138-0142, (2017/08/29)
The present invention relates to a benzisoselenazolone modified nitrosourea compound and applications thereof, wherein the benzisoselenazolone modified nitrosourea compound is represented by a general formula I, has excellent antitumor activity, and can be widely used for preparing antitumor drugs. The general formula I is defined in the specification.
Design, synthesis and evaluation of clioquinol-ebselen hybrids as multi-target-directed ligands against Alzheimer's disease
Wang, Zhiren,Li, Wenrui,Wang, Yali,Li, Xiruo,Huang, Ling,Li, Xingshu
, p. 7139 - 7158 (2016/07/12)
A novel series of compounds obtained by fusing the metal-chelating agent clioquinol and the antioxidant ebselen were designed, synthesized and evaluated as multi-target-directed ligands against Alzheimer's disease (AD). Specifically, compared with their parent compounds clioquinol and ebselen, these hybrids demonstrated significant potency in inhibiting self- and Cu(ii)-induced amyloid-β (Aβ) aggregation and acted as remarkable antioxidants and biometal chelators. In addition, the hybrids showed considerable improvements in ebselen-related pharmacological properties, including the ability to mimic glutathione peroxidase and scavenge H2O2. Of these molecules, compound 10h was identified as a potential lead compound for AD therapy. Importantly, this compound was found to possess rapid H2O2 scavenging activity and glutathione peroxidase-like (GPx-like) activity. Moreover, compound 10h was able to efficiently disassemble preformed self- and Cu(ii)-induced Aβ aggregates. Furthermore, 10h was able to penetrate the central nervous system (CNS) and did not exhibit any acute toxicity in mice at doses up to 2000 mg kg-1.
Computer-assisted designed "selenoxy-chinolin": A new catalytic mechanism of the GPx-like cycle and inhibition of metal-free and metal-associated Aβ aggregation
Wang, Zhiren,Wang, Yali,Li, Wenrui,Liu, Zhihong,Luo, Zonghua,Sun, Yang,Wu, Ruibo,Huang, Ling,Li, Xingshu
, p. 20913 - 20925 (2015/12/11)
Using support from rational computer-assisted design, a novel series of hybrids (selenoxy-chinolin) designed by fusing the metal-chelating agent CQ and the antioxidant ebselen were synthesized and evaluated as multitarget-directed ligands. Most of the hybrids demonstrated significant ability to mimic GPx, which is highly consistent with the prediction results of DFT studies for the selenenyl sulfide intermediates in the computational design. Using 77Se, 1H and 13C NMR spectroscopy and high-resolution mass spectroscopy (HRMS), a novel catalytic mechanism, including a new selenium quinone active species, was first demonstrated. 2D NMR studies indicated that the typical hybrid has an effective interaction with Aβ. In addition, the optimal compound 12k was found to possess an excellent ability to scavenge peroxide and to inhibit self- and metal-induced Aβ aggregation, and an ability to disassemble preformed self- and metal-induced Aβ aggregates effectively. Furthermore, 12k was able to penetrate the central nervous system (CNS) and did not exhibit any acute toxicity in mice at doses up to 2000 mg kg-1. Overall, we demonstrated that hybrid 12k, through rational structure-based computational design, shows a potential for development as a therapeutic agent in AD.
Synthesis and evaluation of multi-target-directed ligands against Alzheimer's disease based on the fusion of donepezil and ebselen
Luo, Zonghua,Sheng, Jianfei,Sun, Yang,Lu, Chuanjun,Yan, Jun,Liu, Anqiu,Luo, Hai-Bin,Huang, Ling,Li, Xingshu
, p. 9089 - 9099 (2014/01/06)
A novel series of compounds obtained by fusing the cholinesterase inhibitor donepezil and the antioxidant ebselen were designed as multi-target-directed ligands against Alzheimer's disease. An in vitro assay showed that some of these molecules did not exhibit highly potent cholinesterase inhibitory activity but did have various other ebselen-related pharmacological effects. Among the molecules, compound 7d, one of the most potent acetylcholinesterase inhibitors (IC50 values of 0.042 μM for Electrophorus electricus acetylcholinesterase and 0.097 μM for human acetylcholinesterase), was found to be a strong butyrylcholinesterase inhibitor (IC50 = 1.586 μM), to possess rapid H2O2 and peroxynitrite scavenging activity and glutathione peroxidase-like activity (ν0 = 123.5 μM min-1), and to be a substrate of mammalian TrxR. A toxicity test in mice showed no acute toxicity at doses of up to 2000 mg/kg. According to an in vitro blood-brain barrier model, 7d is able to penetrate the central nervous system.
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
experimental part, 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.
