The Experts below are selected from a list of 1092 Experts worldwide ranked by ideXlab platform
S H Gillespie - One of the best experts on this subject based on the ideXlab platform.
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identification of 2 Aminothiazole 4 carboxylate derivatives active against mycobacterium tuberculosis h37rv and the β ketoacyl acp synthase mtfabh
PLOS ONE, 2009Co-Authors: Qosay Albalas, Nahoum G. Anthony, Amani Alnimr, Grainne Abbott, Alistair K. Brown, Rebecca C. Taylor, Gurdyal S. Besra, Timothy D. Mchugh, Bilal Aljaidi, S H GillespieAbstract:Tuberculosis (TB) is a disease which kills two million people every year and infects approximately over one-third of the world's population. The difficulty in managing tuberculosis is the prolonged treatment duration, the emergence of drug resistance and co-infection with HIV/AIDS. Tuberculosis control requires new drugs that act at novel drug targets to help combat resistant forms of Mycobacterium tuberculosis and reduce treatment duration. Our approach was to modify the naturally occurring and synthetically challenging antibiotic thiolactomycin (TLM) to the more tractable 2-Aminothiazole-4-carboxylate scaffold to generate compounds that mimic TLM's novel mode of action. We report here the identification of a series of compounds possessing excellent activity against M. tuberculosis H37Rv and, dissociatively, against the β-ketoacyl synthase enzyme mtFabH which is targeted by TLM. Specifically, methyl 2-amino-5-benzylthiazole-4-carboxylate was found to inhibit M. tuberculosis H37Rv with an MIC of 0.06 µg/ml (240 nM), but showed no activity against mtFabH, whereas methyl 2-(2-bromoacetamido)-5-(3-chlorophenyl)thiazole-4-carboxylate inhibited mtFabH with an IC50 of 0.95±0.05 µg/ml (2.43±0.13 µM) but was not active against the whole cell organism. These findings clearly identify the 2-Aminothiazole-4-carboxylate scaffold as a promising new template towards the discovery of a new class of anti-tubercular agents.
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Identification of 2-Aminothiazole-4-Carboxylate Derivatives Active against Mycobacterium tuberculosis H37Rv and the beta-Ketoacyl-ACP Synthase mtFabH
PUBLIC LIBRARY SCIENCE, 2009Co-Authors: Al-balas Q, Ng Anthony, Al-jaidi B, Alnimr A, Abbott G, Ak Brown, Rc Taylor, Gs Besra, Td Mchugh, S H GillespieAbstract:Background: Tuberculosis (TB) is a disease which kills two million people every year and infects approximately over one-third of the world's population. The difficulty in managing tuberculosis is the prolonged treatment duration, the emergence of drug resistance and co-infection with HIV/AIDS. Tuberculosis control requires new drugs that act at novel drug targets to help combat resistant forms of Mycobacterium tuberculosis and reduce treatment duration.Methodology/Principal Findings: Our approach was to modify the naturally occurring and synthetically challenging antibiotic thiolactomycin (TLM) to the more tractable 2-Aminothiazole-4-carboxylate scaffold to generate compounds that mimic TLM's novel mode of action. We report here the identification of a series of compounds possessing excellent activity against M. tuberculosis H37Rv and, dissociatively, against the beta-ketoacyl synthase enzyme mtFabH which is targeted by TLM. Specifically, methyl 2-amino-5-benzylthiazole-4-carboxylate was found to inhibit M. tuberculosis H37Rv with an MIC of 0.06 mu g/ml (240 nM), but showed no activity against mtFabH, whereas methyl 2-(2-bromoacetamido)-5-(3-chlorophenyl)thiazole-4-carboxylate inhibited mtFabH with an IC50 of 0.95 +/- 0.05 mu g/ml (2.43 +/- 0.13 mu M) but was not active against the whole cell organism.Conclusions/Significance: These findings clearly identify the 2-Aminothiazole-4-carboxylate scaffold as a promising new template towards the discovery of a new class of anti-tubercular agents
Qosay Albalas - One of the best experts on this subject based on the ideXlab platform.
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identification of 2 Aminothiazole 4 carboxylate derivatives active against mycobacterium tuberculosis h37rv and the β ketoacyl acp synthase mtfabh
PLOS ONE, 2009Co-Authors: Qosay Albalas, Nahoum G. Anthony, Amani Alnimr, Grainne Abbott, Alistair K. Brown, Rebecca C. Taylor, Gurdyal S. Besra, Timothy D. Mchugh, Bilal Aljaidi, S H GillespieAbstract:Tuberculosis (TB) is a disease which kills two million people every year and infects approximately over one-third of the world's population. The difficulty in managing tuberculosis is the prolonged treatment duration, the emergence of drug resistance and co-infection with HIV/AIDS. Tuberculosis control requires new drugs that act at novel drug targets to help combat resistant forms of Mycobacterium tuberculosis and reduce treatment duration. Our approach was to modify the naturally occurring and synthetically challenging antibiotic thiolactomycin (TLM) to the more tractable 2-Aminothiazole-4-carboxylate scaffold to generate compounds that mimic TLM's novel mode of action. We report here the identification of a series of compounds possessing excellent activity against M. tuberculosis H37Rv and, dissociatively, against the β-ketoacyl synthase enzyme mtFabH which is targeted by TLM. Specifically, methyl 2-amino-5-benzylthiazole-4-carboxylate was found to inhibit M. tuberculosis H37Rv with an MIC of 0.06 µg/ml (240 nM), but showed no activity against mtFabH, whereas methyl 2-(2-bromoacetamido)-5-(3-chlorophenyl)thiazole-4-carboxylate inhibited mtFabH with an IC50 of 0.95±0.05 µg/ml (2.43±0.13 µM) but was not active against the whole cell organism. These findings clearly identify the 2-Aminothiazole-4-carboxylate scaffold as a promising new template towards the discovery of a new class of anti-tubercular agents.
Yaozu Liao - One of the best experts on this subject based on the ideXlab platform.
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synthesis of poly 2 Aminothiazole for selective removal of hg ii in aqueous solutions
Industrial & Engineering Chemistry Research, 2016Co-Authors: Xia Wang, Hua Zou, Yaozu LiaoAbstract:Conducting poly(2-Aminothiazole) (PAT) was simply green synthesized by a chemical oxidation method using 2-Aminothiazole as the monomer and copper chloride as the oxidant in aqueous solution. The effects of reaction time and oxidant/monomer molar ratio on the polymerization yield were investigated. The PATs were characterized by FT-IR, 1H NMR, UV–vis, gel permeation chromatograms (GPC), and scanning electron microscopy (SEM). A series of adsorption experiments were carried out to investigate the adsorption properties of PAT for different heavy metals ions. The results suggested that the PAT possessed much better adsorption capability for Hg(II) than other metal ions. The effects of pH, contact time, and adsorption temperature on the adsorption of Hg(II) were evacuated. The maximum adsorption capacity obtained was 325.7 mg/g at 308 K from the Langmuir model. The adsorption mechanism was studied by FT-IR, UV–vis, and XPS. The polymer could be further regenerated through desorption of Hg(II) using HNO3 or HC...
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Chemical Oxidative Polymerization of 2-Aminothiazole in Aqueous Solution: Synthesis, Characterization and Kinetics Study
MDPI AG, 2016Co-Authors: Hua Zou, Lu Wang, Xia Wang, Yaozu LiaoAbstract:The chemical oxidative polymerization of 2-Aminothiazole (AT) was studied in aqueous solution using copper chloride (CuCl2) as an oxidant. The effect of varying the reaction temperature, reaction time and oxidant/monomer molar ratio on the polymer yield was investigated. The resulting poly(2-Aminothiazole)s (PATs) were characterized by FTIR, 1H NMR, UV-vis, gel permeation chromatography, scanning electron microscopy, thermogravimetric analysis and four-point probe electrical conductivity measurements. Compared with a previous study, PATs with higher yield (81%) and better thermal stability could be synthesized. The chemical oxidative polymerization kinetics of AT were studied for the first time. The orders of the polymerization reaction with respect to monomer concentration and oxidant concentration were found to be 1.14 and 0.97, respectively, and the apparent activation energy of the polymerization reaction was determined to be 21.57 kJ/mol
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Synthesis of Poly(2-Aminothiazole) for Selective Removal of Hg(II) in Aqueous Solutions
2016Co-Authors: Xia Wang, Hua Zou, Yaozu LiaoAbstract:Conducting poly(2-Aminothiazole) (PAT) was simply green synthesized by a chemical oxidation method using 2-Aminothiazole as the monomer and copper chloride as the oxidant in aqueous solution. The effects of reaction time and oxidant/monomer molar ratio on the polymerization yield were investigated. The PATs were characterized by FT-IR, 1H NMR, UV–vis, gel permeation chromatograms (GPC), and scanning electron microscopy (SEM). A series of adsorption experiments were carried out to investigate the adsorption properties of PAT for different heavy metals ions. The results suggested that the PAT possessed much better adsorption capability for Hg(II) than other metal ions. The effects of pH, contact time, and adsorption temperature on the adsorption of Hg(II) were evacuated. The maximum adsorption capacity obtained was 325.7 mg/g at 308 K from the Langmuir model. The adsorption mechanism was studied by FT-IR, UV–vis, and XPS. The polymer could be further regenerated through desorption of Hg(II) using HNO3 or HCl eluent
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simple synthesis of conducting poly 2 Aminothiazole with high molecular weight
Colloid and Polymer Science, 2015Co-Authors: Xia Wang, Hua Zou, Lu Wang, Wei Qian, Yaozu LiaoAbstract:Chemical and electrochemical oxidative polymerizations are the most used methods to synthesize conducting polymers such as polyaniline, polypyrrole, and polythiophene. However, a significant generic problem for these methods is that a high amount of oxidants or electrolytes are needed, which are usually difficult to be removed. Here we report a simple synthesis of conducting poly(2-Aminothiazole) (P2AT) in nitromethane (CH3NO2) using ferric chloride (FeCl3) as an oxidant at a low amount (could be as low as 1 mol%, related to 2-Aminothiazole). The effects of reaction temperature, reaction time, and FeCl3 concentration on the yield of polymerization were systematically investigated. The P2ATs were fully characterized by FT-IR, 1H NMR, UV-vis, gel permeation chromatograms (GPC), and thermogravimetric analysis (TGA). Optimization of the synthetic conditions allows P2AT with both high yield (53 %) and thermal stability (62 % of residue at 600 °C) to be achieved simultaneously. Possible polymerization mechanism was also proposed. Four-probe conductivity measurement indicated that the P2AT exhibited good semi-conductive property with tunable values of 10−5–10−3 S/cm upon iodine (I2) doping. Simple synthesis of P2AT using a low amount of FeCl3 would be a very promising protocol to expand conducting polymer family.
Gabriele Costantino - One of the best experts on this subject based on the ideXlab platform.
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design synthesis and investigation on the structure activity relationships of n substituted 2 Aminothiazole derivatives as antitubercular agents
European Journal of Medicinal Chemistry, 2014Co-Authors: Marco Pieroni, Baojie Wan, Sanghyun Cho, Scott G Franzblau, Gabriele CostantinoAbstract:Abstract Tuberculosis (TB) is one of the deadliest infectious diseases of all times, and its recent resurgence is a supreme matter of concern. Co-infection with HIV and, in particular, the continuous isolation of new resistant strains, makes the discovery of novel anti-TB agents a strategic priority. The research of novel agents should be driven by the accessibility of the synthetic procedure and, in particular, by the lack of cross-resistance with the drugs already marketed. Moreover, in order to shorten the duration of the therapy, and therefore decrease the rate of resistance, these molecules should be active also against the nonreplicating persistent form (NRP-TB) of the infection. The availability of an in-house small library of compounds prompted us to investigate their anti-TB activity. Two compounds, embodying a 2-Aminothiazole scaffold, were found to possess a certain inhibitory activity toward Mycobacterium tuberculosis H 37 Rv, and therefore a medicinal chemistry campaign was initiated in order to increase the activity of the hit compounds and, especially, construct a plausible body of structure–activity relationships. The potency of the hit compound was successfully improved, and, much more importantly, some of the molecules synthesized were found to be active toward the persistent phenotype, and, also, toward a panel of resistant strains. These findings encourage further investigations around this interesting antitubercular chemotype.
David S. Grierson - One of the best experts on this subject based on the ideXlab platform.
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2 Aminothiazole 4 carboxamides enhance readthrough of premature termination codons by aminoglycosides
ACS Medicinal Chemistry Letters, 2019Co-Authors: Safwat M. Rabea, Aruna D. Balgi, Alexandra Krause, Sara Hosseini Farahabadi, Michel Roberge, Alireza Baradaranheravi, David S. GriersonAbstract:Nonsense mutations introduce a premature termination codon (PTC) and are the underlying cause of multiple rare genetic diseases and cancers. Although certain aminoglycosides bind to eukaryotic ribosomes enabling incorporation of an amino acid at the PTC and formation of full-length protein, they are inefficient and toxic at therapeutic doses. Library screening in assays that measure readthrough at a PTC in the TP53 gene in human HDQ-P1 cells identified six novel 2-Aminothiazole-4-carboxamide derivatives that potentiate the PTC readthrough (PTCR) efficiency of G418 when used in combination. The two most potent compounds incorporated a 4-indazole motif on the 2-Aminothiazole nitrogen and a hydrophobic aryl substituent on the carboxamide nitrogen. These compounds are valuable tools to further investigate the therapeutic potential of aminoglycoside-induced PTCR.
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2‑Aminothiazole-4-carboxamides Enhance Readthrough of Premature Termination Codons by Aminoglycosides
2019Co-Authors: Safwat M. Rabea, Alireza Baradaran-heravi, Aruna D. Balgi, Alexandra Krause, Sara Hosseini Farahabadi, Michel Roberge, David S. GriersonAbstract:Nonsense mutations introduce a premature termination codon (PTC) and are the underlying cause of multiple rare genetic diseases and cancers. Although certain aminoglycosides bind to eukaryotic ribosomes enabling incorporation of an amino acid at the PTC and formation of full-length protein, they are inefficient and toxic at therapeutic doses. Library screening in assays that measure readthrough at a PTC in the TP53 gene in human HDQ-P1 cells identified six novel 2-Aminothiazole-4-carboxamide derivatives that potentiate the PTC readthrough (PTCR) efficiency of G418 when used in combination. The two most potent compounds incorporated a 4-indazole motif on the 2-Aminothiazole nitrogen and a hydrophobic aryl substituent on the carboxamide nitrogen. These compounds are valuable tools to further investigate the therapeutic potential of aminoglycoside-induced PTCR
