- A novel potent metal-binding NDM-1 inhibitor was identified by fragment virtual, SPR and NMR screening
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NDM-1 can hydrolyze nearly all available β-lactam antibiotics, including carbapenems. NDM-1 producing bacterial strains are worldwide threats. It is still very challenging to find a potent NDM-1 inhibitor for clinical use. In our study, we used a metal-binding pharmacophore (MBP) enriched virtual fragment library to screen NDM-1 hits. SPR screening helped to verify the MBP virtual hits and identified a new NDM-1 binder and weak inhibitor A1. A solution NMR study of 15N-labeled NDM-1 showed that A1 disturbed all three residues coordinating the second zinc ion (Zn2) in the active pocket of NDM-1. The perturbation only happened in the presence of zinc ion, indicating that A1 bound to Zn2. Based on the scaffold of A1, we designed and synthesized a series of NDM-1 inhibitors. Several compounds showed synergistic antibacterial activity with meropenem against NDM-1 producing K. pneumoniae.
- Bai, Weiqi,Cheng, Kai,Gao, Yan,Guo, Huifang,He, Wei,Li, Conggang,Li, Zhuorong,Wu, Cai
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- Sulfamic acid as a green, reusable catalyst for stepwise, tandem & one-pot solvent-free synthesis of pyrazole derivatives
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Sulfamic acid (SA) is a bi-functional, cost-effective and reusable green catalyst for the synthesis of 4-(pyrazol-4-yl)methylenepyrazol-5(4H)-one derivatives by one-pot, three-component condensation of pyrazol-4-carbaxaldehydes, β-ketoesters and phenyl hydrazine (Route-I). In addition to this method, another simple condensation of pyrazol-4-carbaxaldehydes with pyrazolone in the presence of SA under the solvent-free condition in good yield is reported. The merits of these protocols are mild conditions, non-aqueous workup, high yields, easy availability of the catalyst, no chromatographic separation and inexpensive solid acid catalyst. Furthermore, SA could be recycled and reused for five times without losing its catalytic activity.
- Konkala, Veera Swamy,Dubey, Pramod Kumar
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p. 1571 - 1576
(2017/07/17)
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- Quantification and mass isotopomer profiling of α-keto acids in central carbon metabolism
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Mass spectrometry has been established as a powerful and versatile technique for studying cellular metabolism. Applications range from profiling of metabolites to accurate quantification and tracing of stable isotopes through the biochemical reaction netw
- Zimmermann, Michael,Sauer, Uwe,Zamboni, Nicola
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p. 3232 - 3238
(2014/04/03)
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- Organotin(IV) complexes with pyruvic acid phenylhydrazone (HPAPD): Synthesis, spectral characterization, and invitro antibacterial activity
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The reaction of pyruvic acid phenylhydrazone [HPAPD, (1)] with organotin(IV) chloride(s) leads to the formation of five new organotin(IV) complexes: [MeSnCl2(PAPD)] (2), [BuSnCl2(PAPD)] (3), [PhSnCl2(PAPD)] (4), [Me2
- Salam,Affan,Ahmad, Fasihuddin B.,Arafath, Md. Azharul
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experimental part
p. 1999 - 2007
(2012/09/07)
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- Polyfunctional pyrazoles 5*. preparative synthesis of 1-aryl-4-formylpyrazole- 3-carboxylic acids
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Treatment of methyl pyruvate N-arylhydrazones with the Vilsmeier-Haack reagent gave methyl 1-aryl-4-formylpyrazole-3-carboxylates, basic hydrolysis of which yielded the corresponding acids.
- Bratenko,Barus,Vovk
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experimental part
p. 1464 - 1468
(2010/07/08)
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- α-(1-PHENYLHYDRAZINO)-ALKANONE PHENYLHYDRAZONES: THE REACTION WITH CARBONYL COMPOUNDS
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The unsymmetrically disubstituted hydrazines 1 were condensed with carbonyl compounds.Some of the expected condensation products were isolated, but some were formed as unstable intermediates which underwent 1,4-elimination: The phenylhydrazone of the carbonyl compound used was obtained, together with the corresponding phenylazo-alkene 11 or alternatively, the 1,4-addition product of a different protic nucleophile to 11.
- Schantl, Joachim G.,Karpellus, Peter,Prean, Michael
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p. 5807 - 5814
(2007/10/02)
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- A CONVENIENT SYNTHESIS OF 1-ARYL-Δ2-1,2,4-TRIAZOLIN-5-ONES FROM ARYLHYDRAZINES
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1-Aryl-1,2,4-triazolin-5-ones are prepared from arylhydrazones of α-keto acids by treatment with diphenylphosphoryl azide.
- Lyga, John W.
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p. 163 - 168
(2007/10/02)
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