1381782-06-4

Upstream product

• 394-31-0 2-amino-5-hydroxybenzoic acid 
• 1239668-62-2 5,5'-dihydroxy-(2,2'-diselenobisbenzoic acid) 
• 1381782-05-3 5,5'-diacetoxy-(2,2'-diselenobisbenzoic acid) 

Relevant academic research and scientific papers

Design, synthesis, and biological evaluation of histone deacetylase inhibitors possessing glutathione peroxidase-like and antioxidant activities against Alzheimer's disease

A series of hybrids containing the pharmacophores of the histone deacetylase (HDAC) inhibitor, SAHA, and the antioxidant ebselen were designed and synthesized as multi-target-directed ligands against Alzheimer's disease. An in vitro assay indicated that some of these molecules exhibit potent HDAC inhibitory activity and ebselen-related pharmacological effects. Specifically, the optimal compound 7f was found to be a potent HDAC inhibitor (IC50 = 0.037 μM), possessing rapid hydrogen peroxide scavenging activity and glutathione peroxidase-like activity (ν0 = 150.0 μM min?1) and good free oxygen radical absorbance capacity (value of ORAC: 2.2). Furthermore, compound 7f showed significant protective effects against damage induced by H2O2 and the ability to prevent ROS accumulation in PC12 cells.

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

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.

Computer-assisted designed "selenoxy-chinolin": A new catalytic mechanism of the GPx-like cycle and inhibition of metal-free and metal-associated Aβ aggregation

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.

Inhibition of thioredoxin reductase by a novel series of bis-1,2-benzisoselenazol-3(2H)-ones: Organoselenium compounds for cancer therapy

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.