Design and synthesis of 2-aminothiazole based antimicrobials targeting MRSA

Annadurai, Sivakumar; Martinez, Rogelio L.; Canney, Daniel J.; Eidem, Tess M.; Dunman, Paul M.; Abou‐Gharbia, Magid

doi:10.1016/j.bmcl.2012.09.095

Cited by 42 publications

(20 citation statements)

References 18 publications

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“…The generality of protocol was evaluated across a wide variety of ketones and it was found that phenylethanones with an electron-donating substituent were more efficient as compared to those with an electron-withdrawing substituent on the phenyl ring ( Table 2, entries 2-6 vs 7-9). Moreover, heterocyclic and aliphatic ketones were also well compatible with the present reaction conditions ( Table 2, entries [11][12][13][14].…”

mentioning

confidence: 62%

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Carbon tetrabromide mediated oxidative cyclocondensation of ketones and thioureas: an easy access to 2-aminothiazoles

Keshari

Kapoorr

Yadav

2015

Tetrahedron Letters

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mentioning

confidence: 62%

“…entry 1 vs[12][13][14]. CH 3 CN was found the most suitable solvent among CH 3 CN, THF, DMF, CH 2 Cl 2 and C 2 H 5 OH(Table 1, entry 1 vs 4-7).…”

mentioning

confidence: 96%

Carbon tetrabromide mediated oxidative cyclocondensation of ketones and thioureas: an easy access to 2-aminothiazoles

Keshari

Kapoorr

Yadav

2015

Tetrahedron Letters

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“…Mechanism-of-action studies suggested that 2-aminoarylthiazoles improved DF508-CFTR folding at the ER and stability at the cell surface (Loo et al, 2013). Recent reported biologic activities of aminothiazoles include inhibition of prion replication (Gallardo-Godoy et al, 2011), antimicrobial activity against methicillin-resistant Staphylococcus aureus (Annadurai et al, 2012), and g-secretase modulators for treatment of Alzheimer disease (Lübbers et al, 2011). Similar dihydrospiro-indenes (class H) have been reported as inhibitors of Enterococcus faecalis and S. aureus phenylalanyl-transfer RNA synthetases with low nanomolar potency (Yu et al, 2004).…”

Section: Vx-809 In Transfected Cfbe41omentioning

confidence: 99%

Synergy-Based Small-Molecule Screen Using a Human Lung Epithelial Cell Line Yields ΔF508-CFTR Correctors That Augment VX-809 Maximal Efficacy

Phuan¹,

Veit²,

Tan³

et al. 2014

Mol Pharmacol

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The most prevalent cystic fibrosis transmembrane conductance regulator (CFTR) mutation causing cystic fibrosis, DF508, impairs folding of nucleotide binding domain (NBD) 1 and stability of the interface between NBD1 and the membranespanning domains. The interfacial stability defect can be partially corrected by the investigational drug Second-generation DF508-CFTR correctors are needed to improve on the modest efficacy of existing cystic fibrosis correctors. We postulated that a second corrector targeting a distinct folding/interfacial defect might act in synergy with VX-809 or the R1070W suppressor mutation. A biochemical screen for DF508-CFTR cell surface expression was developed in a human lung epithelium-derived cell line (CFBE41o 2 ) by expressing chimeric CFTRs with a horseradish peroxidase (HRP) in the fourth exofacial loop in either the presence or absence of R1070W. Using a luminescence readout of HRP activity, screening of approximately 110,000 small molecules produced nine novel corrector scaffolds that increased cell surface ΔF508-CFTR expression by up to 200% in the presence versus absence of maximal VX-809. Further screening of 1006 analogs of compounds identified from the primary screen produced 15 correctors with an EC 50 , 5 mM. Eight chemical scaffolds showed synergy with VX-809 in restoring chloride permeability in ΔF508-expressing A549 cells. An aminothiazole increased chloride conductance in human bronchial epithelial cells from a DF508 homozygous subject beyond that of maximal VX-809. Mechanistic studies suggested that NBD2 is required for the aminothiazole rescue. Our results provide proof of concept for synergy screening to identify second-generation correctors, which, when used in combination, may overcome the "therapeutic ceiling" of first-generation correctors.

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“…anti-cancer 18,19, herbicidal activity 20 , mitochondrial apoptotic inducers 21 , neuronal nitric oxide synthase inhibitor 22 , anti-inflammatory 23,24 , antimalarials 25 , antimicrobial 26,27 .…”

Section: Introductionmentioning

confidence: 99%

An Aerobic Oxidative Coupling Approach for The Synthesis of N-Substituted 2-Aminobenzothiazole Derivatives using Iron Catalyst

N¹,

Kamath²,

Gaonkar³

et al. 2016

Orient. J. Chem

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A facile and convenient method was developed for the formation of novel N substituted 2-aminobenzothiazoles via an iron-catalysed condensation of 2-aminobenzothizole with different amines. This method is applicable for a wide range of aliphatic, aromatic and heterocyclic amines furnishing moderate yields of the corresponding products and thus rendering the methodology as a highly eco-friendly, inexpensive alternative to the existing methods.

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Design and synthesis of 2-aminothiazole based antimicrobials targeting MRSA

Cited by 42 publications

References 18 publications

Carbon tetrabromide mediated oxidative cyclocondensation of ketones and thioureas: an easy access to 2-aminothiazoles

Carbon tetrabromide mediated oxidative cyclocondensation of ketones and thioureas: an easy access to 2-aminothiazoles

Synergy-Based Small-Molecule Screen Using a Human Lung Epithelial Cell Line Yields ΔF508-CFTR Correctors That Augment VX-809 Maximal Efficacy

An Aerobic Oxidative Coupling Approach for The Synthesis of N-Substituted 2-Aminobenzothiazole Derivatives using Iron Catalyst

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