78573-36-1Relevant academic research and scientific papers
Degradation of MAC13243 and studies of the interaction of resulting thiourea compounds with the lipoprotein targeting chaperone LolA
Barker, Courtney A.,Allison, Sarah E.,Zlitni, Soumaya,Nguyen, Nick Duc,Das, Rahul,Melacini, Giuseppe,Capretta, Alfredo A.,Brown, Eric D.
, p. 2426 - 2431 (2013/05/21)
The discovery of novel small molecules that function as antibacterial agents or cellular probes of biology is hindered by our limited understanding of bacterial physiology and our ability to assign mechanism of action. We previously employed a chemical genomic strategy to identify a novel small molecule, MAC13243, as a likely inhibitor of the bacterial lipoprotein targeting chaperone, LolA. Here, we report on the degradation of MAC13243 into the active species, S-(4-chlorobenzyl)isothiourea. Analogs of this compound (e.g., A22) have previously been characterized as inhibitors of the bacterial actin-like protein, MreB. Herein, we demonstrate that the antibacterial activity of MAC13243 and the thiourea compounds are similar; these activities are suppressed or sensitized in response to increases or decreases of LolA copy number, respectively. We provide STD NMR data which confirms a physical interaction between LolA and the thiourea degradation product of MAC13243, with a K d of ～150 μM. Taken together, we conclude that the thiourea series of compounds share a similar cellular mechanism that includes interaction with LolA in addition to the well-characterized target MreB.
Fluorescence resonance energy transfer (FRET) as a high-throughput assay for coupling reactions. Arylation of amines as a case study
Stauffer, Shaun R.,Hartwig, John F.
, p. 6977 - 6985 (2007/10/03)
A solution-phase assay based on fluorescence resonance energy transfer (FRET) was developed for high-throughput screening of palladium catalyzed aminations of aryl halides. Dansylpiperazine was used as the fluorescent component and a chloro- or bromoarene tagged with an azodye as the quenching partner. Fluorescence intensities of reaction aliquots correlated linearly with reaction yield after dilution to appropriate concentrations. A library of 119 phosphine and heterocyclic carbene ligands was evaluated in duplicate reactions of two combinations. In general, the FRET assay displayed excellent reproducibility, with less than 5% of the duplicate experiments showing significant variability in yields. Among reactions producing greater than 50% yield, the average percent uncertainty was just 5%. For a small subset of sterically hindered ligands, differences in yields between 10 and 20% were observed between the substrates bearing dyes for the FRET assay and substrates that are unfunctionalized. However, the remaining catalyst combinations gave yields similar to those expected from literature precedent. In addition to an evaluation of the accuracy of the FRET assay, this work includes the use of the FRET assay to investigate relative activities of various catalysts for the amination of aryl bromides and chlorides and to find conditions for aminations in more polar solvents. Reactions with K3PO4 base in aqueous mixtures of polar and nonpolar organic solvents were shown to be appropriate for the amination chemistry.
Substituted oxiranecarboxylic acids, their use and medicaments containing them
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, (2008/06/13)
Substituted oxiranecarboxylic acids of the formula STR1 wherein R1 denotes a hydrogen atom (--H), a halogen atom, a hydroxylroup, a lower alkyl group, a lower alkoxy group or a trifluoromethyl group, R2 has one of the meanings of Rs
Substituted oxocarboxylic acids, processes for their preparation, their use and medicaments containing them
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, (2008/06/13)
Substituted oxocarboxylic acids of the formula I STR1 wherein R1 denotes a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkyl group, a lower alkoxy group or a trifluoromethyl group, R2 denotes a hydrogen atom or a halogen atom and n denotes an integer from 3 to 8, and their salts display a hypoglycaemic action in warm-blooded animals. Processes for the preparation of the new compounds and of the intermediate products required for their preparation, as well as of the corresponding medicaments are described.
