- A Cephalosporin Prochelator Inhibits New Delhi Metallo-β-lactamase 1 without Removing Zinc
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Antibacterial drug resistance is a rapidly growing clinical threat, partially due to expression of β-lactamase enzymes, which confer resistance to bacteria by hydrolyzing and inactivating β-lactam antibiotics. The increasing prevalence of metallo-β-lactamases poses a unique challenge, as currently available β-lactamase inhibitors target the active site of serine β-lactamases but are ineffective against the zinc-containing active sites of metallo-β-lactamases. There is an urgent need for metallo-β-lactamase inhibitors and antibiotics that circumvent resistance mediated by metallo-β-lactamases in order to extend the utility of existing β-lactam antibiotics for treating infection. Here we investigated the antibacterial chelator-releasing prodrug PcephPT (2-((((6R,7R)-2-carboxy-8-oxo-7-(2-phenylacetamido)-5-thia-1-azabicyclo[4.2.0]-oct-2-en-3-yl)methyl)thio) pyridine 1-oxide) as an inhibitor of New Delhi metallo-β-lactamase 1 (NDM-1). PcephPT is an experimental compound that we have previously shown inhibits growth of β-lactamase-expressing E. coli using a mechanism that is dependent on both copper availability and β-lactamase expression. Here, we found that PcephPT, in addition to being a copperdependent antibacterial compound, inhibits hydrolysis activity of purified NDM-1with an IC50 of 7.6 ìM without removing zinc from the active site and restores activity of the carbapenem antibiotic meropenem against NDM-1-producing E. coli. This work demonstrates that targeting a metal-binding pharmacophore to β-lactamase-producing bacteria is a promising strategy for inhibition of both bacterial growth and metallo-β-lactamases.
- Jackson, Abigail C.,Zaengle-Barone, Jacqueline M.,Puccio, Elena A.,Franz, Katherine J.
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- Synthesis method of zinc pyrithione
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The invention discloses a synthesis method of zinc pyrithione, and belongs to the field of organic synthesis. According to the synthesis method, 2-chloropyridine is used as a raw material; a final product is obtained through three steps of reactions of nitrogen oxidation, sulfhydrylation and salt formation. The synthesis method is simple in step and convenient to operate and further, the content of an obtained product is high.
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Paragraph 0033; 0034; 0035; 0036; 0037; 0038; 0039; 0040
(2018/04/02)
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- A Simple and Efficient Method for the Preparation of Heterocyclic N-Oxide
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Pyridine, 2-methylpyridine, 3-methylpyridine, 4-methylpyridine, 2,4-dimethylpyridine, 2,6-dimethylpyridine, quinoline, isoquinoline and 2-chloropyridine are readily oxidized to their N-oxides with a solution of trichloroisocyanuric acid, acetic acid, sodium acetate and water in acetonitrile and methylene dichloride in 78%-90% yields.
- Zhong, Ping,Guo, Sheng-Rong,Song, Cai-Sheng
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p. 247 - 253
(2007/10/03)
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- Antivesicant compounds and methods of making and using thereof
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As disclosed herein, the present invention provides a compound having the structural formula wherein R1, R2, R3, and R4 are each independently H, or a methyl, halo, trifluoromethyl, nitro, alkyloxy, or acyloxy group, or a pharmaceutically acceptable salt or prodrug thereof. Also disclosed are compounds, compositions, methods and kits for treating, preventing, or inhibiting injuries induced by a vesicant agent, such as bis-2-chloroethylsulfide (HD). Additionally, protectants and decontaminants are disclosed.
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- Process for the manufacture of 2-mercapto pyridine-1-oxides
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A process for the manufacture of 2-mercaptopyridine-1-oxides and zinc salts thereof, comprising the steps of oxidizing a 2-acetylaminopyridine with peracetic acid in an inert solvent to give a 2-acetamidopyridine-1-oxide, cleaving the acetyl group with mineral acid to give a 2-aminopyridine-1-oxide, diazotizing the 2-aminopyridine-1-oxide and treating the diazonium salt with hydrochloric acid to give a 2-chloropyridine-1-oxide, treating the latter with a sulfhydryl-donor to give a 2-mercaptopyridine-1-oxide, and optionally treating the latter with a zinc salt to make the 2:1 zinc salt of the 2-mercaptopyridine-1-oxide. The resulting zinc salts are useful in anti-dandruff preparations.
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