4322-93-4

Upstream product

• 19602-82-5 2,2'-dithiodibenzoic acid dichloride 
• 619-45-4 4-methoxycarbonyl aniline 
• 3950-02-5 2-chlorosulfenylbenzoyl chloride 
• 119-80-2 2,2'-dithiobenzoic acid 
• 1309368-64-6 methyl 4-(2-mercaptobenzamido)benzoate 
• 88-67-5 2-Iodobenzoic acid 
• 310453-98-6 methyl 4-(2-iodobenzamido)benzoate 
• 609-67-6 2-Iodobenzoyl chloride 

Downstream Products

• 78492-51-0 2-(4-carbossifenil)-3-oxo-2,3-diidro-1,2-benzisotiazolo-1,1-diossido 
• 130266-97-6 4-(3-Oxo-3H-benzo[d]isothiazol-2-yl)-benzoyl chloride 
• 37006-81-8 4-(3-oxo-1,2-benzisotiazolin-2-il)benzamide 
• 102486-62-4 2-(4-metossicarbonilfenil)-3-oxo-2,3-diidro-1,2-benzisotiazolo-1,1-diossido 

Relevant academic research and scientific papers

Ebsulfur as a potent scaffold for inhibition and labelling of New Delhi metallo-β-lactamase-1 in vitro and in vivo

The superbug infection caused by New Delhi metallo-β-lactamase (NDM-1) has grown into an emerging threat, labelling and inhibition of NDM-1 has proven challenging due to its shuttling between pathogenic bacteria. Here, we report a potent covalent scaffold, ebsulfur, for targeting the protein in vitro and in vivo. Enzymatic kinetic study indicated that eighteen ebsulfurs gained except 1a–b and 1f inhibited NDM-1, exhibiting an IC50 value ranging of 0.16–9 μM, and 1g was found to be the best, dose- and time-dependent inhibitor with an IC50 of 0.16 μM. Also, these ebsulfurs effectively restored the antibacterial activity of cefazolin against E. coli expressing NDM-1, and the best effect was observed to be from 1g, 1i and 1n, resulting in an 256-fold reduction in MIC of the antibiotic at a dose of 16 μg/mL. The equilibrium dialysis study implied that the ebsulfur disrupted the coordination of one Zn(II) ion at active site of NDM-1. Labelling of NDM-1 using a constructed fluorescent ebsulfur Ebs-R suggested that the inhibitor covalently bound to the target through SDS-PAGE analysis in vitro. Also, labelling NDM-1 in living E. coli cells with Ebs-R by confocal microscopic imaging showed the real-time distribution change process of intracellular recombinant protein NDM-1. Moreover, the cytotoxicity of these ebsulfurs against L929 mouse fibroblastic cells was tested, and their capability to restore antibacterial activity of antibiotic against clinical strains E. coli EC08 producing NDM-1 was determined. The ebsulfur scaffold proposed here is valuable for development of the covalent irreversible inhibitors of NDM-1, and also for labelling the target in vitro and in vivo.

Evaluation of substituted ebselen derivatives as potential trypanocidal agents

Human African trypanosomiasis is a disease of sub-Saharan Africa, where millions are at risk for the illness. The disease, commonly referred to as African sleeping sickness, is caused by an infection by the eukaryotic pathogen, Trypanosoma brucei. Previously, a target-based high throughput screen revealed ebselen (EbSe), and its sulfur analog, EbS, to be potent in vitro inhibitors of the T. brucei hexokinase 1 (TbHK1). These molecules also exhibited potent trypanocidal activity in vivo. In this manuscript, we synthesized a series of sixteen EbSe and EbS derivatives bearing electron-withdrawing carboxylic acid and methyl ester functional groups, and evaluated the influence of these substituents on the biological efficacy of the parent scaffold. With the exception of one methyl ester derivative, these modifications ablated or blunted the potent TbHK1 inhibition of the parent scaffold. Nonetheless, a few of the methyl ester derivatives still exhibited trypanocidal effects with single-digit micromolar or high nanomolar EC50values.

INHIBITORS OF NOX ENZYMES AND METHODS OF USE THEREOF

Inhibitors of Nox enzymes, such as Noxl, Nox2, and Nox3, and methods of making and using such compounds are describe herein.