110045-70-0Relevant articles and documents
Haloperoxidase mediated quorum quenching by Nitzschia cf pellucida: Study of the metabolization of N-Acyl homoserine lactones by a benthic diatom
Syrpas, Michail,Ruysbergh, Ewout,Blommaert, Lander,Vanelslander, Bart,Sabbe, Koen,Vyverman, Wim,De Kimpe, Norbert,Mangelinckx, Sven
, p. 352 - 367 (2014)
Diatoms are known to produce a variety of halogenated compounds, which were recently shown to have a role in allelopathic interactions between competing species. The production of these compounds is linked to haloperoxidase activity. This research, has shown that this system may also be involved in diatom-bacteria interactions via the H2O2 dependent inactivation of a type of quorum sensing (QS) molecule, i.e., N-β-ketoacylated homoserine lactones (AHLs), by a natural haloperoxidase system from the benthic diatom Nitzschia cf pellucida. The AHL degradation pathway towards corresponding halogenated derivatives was elucidated via HPLC-MS analysis and the synthesis of a broad series of novel halogenated AHL analogues as reference compounds. Furthermore, their biological activity as quorum sensing modulators was directly compared and evaluated against a series of naturally occurring β-keto-AHLs. It has been demonstrated that the loss of the QS activity results from the final cleavage of the halogenated N-acyl chain of the signal molecules.
An unprecedented medium-chain diunsaturated n-acylhomoserine lactone from marine roseobacter group bacteria
Ziesche, Lisa,Wolter, Laura,Wang, Hui,Brinkhoff, Thorsten,Pohlner, Marion,Engelen, Bert,Wagner-D?bler, Irene,Schulz, Stefan
, (2019)
N-acylhomoserine lactones (AHLs), bacterial signaling compounds involved in quorum-sensing, are a structurally diverse group of compounds. We describe here the identification, synthesis, occurrence and biological activity of a new AHL, N-((2E,5Z)-2,5-dodecadienoyl)homoserine lactone (11) and its isomer N-((3E,5Z)-3,5-dodecadienoyl)homoserine lactone (13), occurring in several Roseobacter group bacteria (Rhodobacteraceae). The analysis of 26 strains revealed the presence of 11 and 13 in six of them originating from the surface of the macroalgae Fucus spiralis or sediments from the North Sea. In addition, 18 other AHLs were detected in 12 strains. Compound identification was performed by GC/MS. Mass spectral analysis revealed a diunsaturated C12 homoserine lactone as structural element of the new AHL. Synthesis of three likely candidate compounds, 11, 13 and N-((2E,4E)-2,4-dodecadienoyl)homoserine lactone (5), revealed the former to be the natural AHLs. Bioactivity test with quorum-sensing reporter strains showed high activity of all three compounds. Therefore, the configuration and stereochemistry of the double bonds in the acyl chain seemed to be unimportant for the activity, although the chains have largely different shapes, solely the chain length determining activity. In combination with previous results with other Roseobacter group bacteria, we could show that there is wide variance between AHL composition within the strains. Furthermore, no association of certain AHLs with different habitats like macroalgal surfaces or sediment could be detected.
Small Molecule Inhibitors of the PCSK9·LDLR Interaction
Taechalertpaisarn, Jaru,Zhao, Bosheng,Liang, Xiaowen,Burgess, Kevin
supporting information, p. 3242 - 3249 (2018/03/13)
The protein-protein interaction between proprotein convertase subtilisin/kexin type 9 (PCSK9) and low-density lipoprotein receptor (LDLR) is a relatively new, and extremely important, validated therapeutic target for treatment and prevention of heart disease. Experts in the area agree that the first small molecules to disrupt PCSK9·LDLR would represent a milestone in this field, yet few credible leads have been reported. This paper describes how side-chain orientations in preferred conformations of carefully designed chemotypes were compared with LDLR side chains at the PCSK9·LDLR interface to find molecules that would mimic interface regions of LDLR. This approach is an example of the procedure called EKO (Exploring Key Orientations). The guiding hypothesis on which EKO is based is that good matches indicate the chemotypes bearing the same side chains as the protein at the sites of overlay have the potential to disrupt the parent protein-protein interaction. In the event, the EKO procedure and one round of combinatorial fragment-based virtual docking led to the discovery of seven compounds that bound PCSK9 (SPR and ELISA) and had a favorable outcome in a cellular assay (hepatocyte uptake of fluorescently labeled low-density lipoprotein particles) and increased the expression LDLR on hepatocytes in culture. Three promising hit compounds in this series had dissociation constants for PCSK9 binding in the 20-40 μM range, and one of these was modified with a photoaffinity label and shown to form a covalent conjugate with PCSK9 on photolysis.
Design, synthesis and activity evaluation study of novel substituted N-sulfonyl homoserine lactone derivatives as bacterial quorum sensing inhibitors
Sun, Qi,Zhao, Mingming,Liang, Jingwei,Xiao, Junhai,Meng, Fanhao
, p. 3345 - 3353 (2017/11/16)
A novel series of N-sulfonyl homoserine lactone derivatives 7a–7m has been designed, synthesized, and evaluated for quorum sensing inhibitory activities through the violacein inhibition in Chromobacterium violaceum CV026. Compound 7e displayed the high level of inhibitory activity among all the compounds synthesized. Studies of structure-activity relationship indicated that compounds with thiophene group in side chain showed better activity than those substituted by furan, pyrrole, pyridyl, and phenethyl group. Thiophene substituted compounds which connected electron withdrawing group exhibited better inhibitory activity relate to those connected electron donating group. Further analysis indicated that compound bearing an electron withdrawing substituent at the position 2 of their thiophene ring exhibited superior activity against violacein production to those bearing the substituent at the position 3 and 4. Compound 7e in particular, with IC50 value of 6.19 μM, were identified as promising lead compounds for further development.
