- Azolylthioacetamides as a potent scaffold for the development of metallo-β-lactamase inhibitors
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In an effort to develop new inhibitors of metallo-β-lactamases (MβLs), twenty-eight azolylthioacetamides were synthesized and assayed against MβLs. The obtained benzimidazolyl and benzioxazolyl substituted 1–19 specifically inhibited the enzyme ImiS, and 10 was found to be the most potent inhibitor of ImiS with an IC50 value of 15 nM. The nitrobenzimidazolyl substituted 20–28 specifically inhibited NDM-1, with 27 being the most potent inhibitor with an IC50 value of 170 nM. Further studies with 10, 11, and 27 revealed a mixed inhibition mode with competitive and uncompetitive inhibition constants in a similar range as the IC50 values. These inhibitors resulted in a 2–4-fold decrease in imipenem MIC values using E. coli cells producing ImiS or NDM-1. While the source of uncompetitive (possibly allosteric) inhibition remains unclear, docking studies indicate that 10 and 11 may interact orthosterically with Zn2 in the active site of CphA, while 27 could bridge the two Zn(II) ions in the active site of NDM-1 via its nitro group.
- Xiang, Yang,Chang, Ya-Nan,Ge, Ying,Kang, Joon S.,Zhang, Yi-Lin,Liu, Xiao-Long,Oelschlaeger, Peter,Yang, Ke-Wu
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supporting information
p. 5225 - 5229
(2017/11/13)
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- Synthetic studies and antibacterial activity of nucleobases and their N- and S-glucosides from 2-amino benzoic acid and its benzamido derivatives
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A series of S-glucosides 11a-14a and their benzamido derivatives 11b-14b have been synthesized by reacting D-glucose with thiol groups of 5-(2′-aminophenylene)-1,3,4-oxadiazole-2-thioles 7(a,b), 5-(2′-aminophenylene)-1,3,4-thiadiazole-2-thiols 8(a,b), 5-(2′-aminophenylene)-1,2,4-triazole-3-thiols 9(a,b) and 5-(2′-aminophenylene)-4-N-amino-1,2,4-triazole-3-thiols 10(a,b). The thiols 7(a,b)-10(a,b) have been synthesized from hydrazides 3(a,b) which already been synthesized from 2-aminobenzoic acid and its benzamido derivative. All synthesized compounds were characterized by IR, UV,1H- and13C- NMR. Nucleobases and a representative of S-glycoside were tested in vitro against the following microorganisms: two Gram-positive bacteria Staphylococcus aureus and Bacillus cereusand two Gram-negative bacteria Escherichia coli, Pseudomonas aeruginosa and they exhibited significant effects. Amykacine was used as positive standard.
- Benhammadi, Samia,Iraten, Salima,Othman, Adil A.
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p. 2567 - 2576
(2016/11/22)
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- Combinatorial approach: Identification of potential antifungals from triazole minilibraries
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Employing basic principles of solution phase combinatorial chemistry, a solution phase combinatorial synthesis and screening of mini libraries of 1,2,4-triazole derivatives has been carried out. 6 x 6 indexed mini libraries were synthesized comprising of 36 compounds. The libraries were analyzed by liquid chromatography - mass spectrometry - mass spectrometry (LC - MS - MS) analysis. All the synthesized mini libraries were screened for antifungal activity and by deconvolution methodology leads for every fungi used for study were identified. The leads were synthesized individually and screened for activity. The antifungal activity of individually synthesized leads was improved as anticipated, in comparison with that of any of the mini libraries. Springer Science+Business Media, LLC 2010.
- Bhatia, Manish Sudesh,Zarekar, Bandu Eknath,Choudhari, Prafulla Balkrishna,Ingale, Kundan Bhanudas,Bhatia, Neela Manish
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experimental part
p. 116 - 120
(2012/03/10)
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- Studies on organophosphorus compounds. Synthesis and reactions of 1,2,4-triazolo(4,3-d)-1,3,4,2-benzo-oxadiazaphosphopine and triazaphosphopine derivatives
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2,4-Bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulphide (Lawesson's Reagent, LR) reacted with 4-amino-3-mercapto-5-(o-hydroxyphenyl and/or o-aminophenyl)-1,2,4-triazoles (1a and 2a) in boiling acetonitrile to afford s-triazolo(4,3-d)-1,3,4,2-b
- Moustafa
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p. 131 - 142
(2007/10/03)
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- Cytoprotection utilizing aryltriazol-3-thiones
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5-Aryltriazol-3-thiones are useful for inhibiting adhesion of Mac-1 and thereby providing cytoprotection for diseases mediated by Mac-1 adhesion.
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- Synthesis and a UV and IR spectral study of some 2-aryl-Δ2-1,3,4-oxadiazoline-5-thiones
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Twenty four 2-aryl-Δ2-1,3,4-oxadiazoline-5-thione derivatives 2 were synthesized and their uv and ir spectra were studied. Correlation between σ-Hammett constants of aryl substituents and the differences in absorption maxima (Δν = ν1-ν2 in kK) of the electronic spectra of the deprotonated species were also evaluated. A new method for the synthesis of the 2-(amino)aryl derivatives 2v,w,x is also reported.
- Charistos,Vagenas,Tzavellas,Tsoleridis,Rodios
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p. 1593 - 1598
(2007/10/02)
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