13283-92-6Relevant articles and documents
Seven new didemnins from the marine tunicate Trididemnum solidum
Sakai, Ryuichi,Stroh, Justin G.,Sullins, David W.,Rinehart, Kenneth L.
, p. 3734 - 3748 (1995)
Seven new didemnins-didemnins M (1), N (2), X (3) and Y (4), nordidemnin N (5), epididemnin A1 (6), and acyclodidemnin A (7)-were isolated from an extract of the Caribbean tunicate Trididemnum solidum. The structures of these compounds were assigned, based on FABMS, high-field NMR data, and chemical degradation studies. Biological activities of these peptides are also described.
Synthesis and absolute configuration of syringolide 2, an elicitor from Pseudomonas syringae pv. tomato
Kuwahara, Shigefumi,Moriguchi, Masahiko,Miyagawa, Kazuhiro,Konno, Masako,Kodama, Osamu
, p. 3201 - 3202 (1995)
The enantioselective synthesis of syringolide 2, one of the two elicitors produced by Pseudomonas syringae pv. tomato, was accomplished in 11 steps from diethyl D-tartrate.
Structure-Activity Relationship Study of Majusculamides A and B and Their Analogues on Osteogenic Activity
Nakajima, Daisuke,Natsume, Noriyuki,Ozaki, Kaori,Teruya, Toshiaki,Yokoshima, Satoshi
, p. 2477 - 2482 (2020/10/02)
We discovered that majusculamide A (1) and majusculamide B (2), isolated from a marine cyanobacterium collected in Okinawa, induced osteoblast differentiation in MC3T3-E1 cells. Although majusculamide A (1) has a different configuration only at the C-19 stereocenter, bearing a methyl group, compared to majusculamide B (2), the effect of 1 was stronger than that of 2. We synthesized some analogues of the majusculamides (3-15) and evaluated osteogenic activities of these analogues. The structure-activity relationship study of majusculamide analogues suggested that the number of methyls and configuration at C-19 and the nature of the substituent at C-20 of majusculamide A (1) may be important for the osteoblast differentiation-inducing effect of 1.
MACROCYCLIC BROAD SPECTRUM ANTIBIOTICS
-
Paragraph 00848, (2017/08/01)
Provided herein are antibacterial compounds, wherein the compounds in some embodiments have broad spectrum bioactivity. In various embodiments, the compounds act by inhibition of bacterial type 1 signal peptidase (SpsB), an essential protein in bacteria. Pharmaceutical compositions and methods for treatment using the compounds described herein are also provided.
A Continuous, Fluorogenic Sirtuin 2 Deacylase Assay: Substrate Screening and Inhibitor Evaluation
Galleano, Iacopo,Schiedel, Matthias,Jung, Manfred,Madsen, Andreas S.,Olsen, Christian A.
supporting information, p. 1021 - 1031 (2016/02/23)
Sirtuins are important regulators of lysine acylation, which is implicated in cellular metabolism and transcriptional control. This makes the sirtuin class of enzymes interesting targets for development of small molecule probes with pharmaceutical potential. To achieve detailed profiling and kinetic insight regarding sirtuin inhibitors, it is important to have access to efficient assays. In this work, we report readily synthesized fluorogenic substrates enabling enzyme-economical evaluation of SIRT2 inhibitors in a continuous assay format as well as evaluation of the properties of SIRT2 as a long chain deacylase enzyme. Novel enzymatic activities of SIRT2 were thus established in vitro, which warrant further investigation, and two known inhibitors, suramin and SirReal2, were profiled against substrates containing ε-N-acyllysine modifications of varying length.
Design and Synthesis of 2-Alkylpyrimidine-4,6-diol and 6-Alkylpyridine-2,4-diol as Potent GPR84 Agonists
Liu, Yang,Zhang, Qing,Chen, Lin-Hai,Yang, Hui,Lu, Wei,Xie, Xin,Nan, Fa-Jun
supporting information, p. 579 - 583 (2016/07/06)
A series of alkylpyrimidine-4,6-diol derivatives were designed and synthesized as novel GRP84 agonists based on a high-throughput screening (HTS) hit 1. 6-Nonylpyridine-2,4-diol was identified as the most potent agonist of GPR84 reported so far, with an EC50 of 0.189 nM. These novel GPR84 agonists will provide valuable tools for the study of the physiological functions of GPR84.
Synthesis of tritium labelled and photoactivatable N-acyl-L-homoserine lactones: Inter-kingdom signalling molecules
Jakubczyk, Dorota,Brenner-Weiss, Gerald,Braese, Stefan
, p. 592 - 597 (2014/02/14)
N-Acyl-L-homoserine lactones (AHLs) are signal molecules that are synthesized in nature by Gram-negative bacteria. They allow communication between bacteria (quorum sensing) and between microorganisms and their eukaryotic host cells (inter-kingdom signalling). However, very little is known about the mechanisms of the latter system. Therefore, tritium labelled photoactivatable AHLs were synthesized to identify specific receptors in immune cells (e.g., human polymorphonuclear neutrophils, PMN) that bind to AHL. A photoaffinity label - a diazirine group - was chosen as the smallest possible photoactivatable group that can be activated by light irradiation. The resulting highly active carbene will bind covalently to the closest chemical structure in the pocket of the receptor. The diazirine label was introduced into the AHL molecule according to a literature method. To isolate the labelled receptor from the cellular protein moiety, the AHL was additionally labelled with tritium. During the development of an effective isotopic labelling method, a simple route to hydrogen isotope incorporation into the AHLs was proposed and explored in detail. According to the new protocol, the photoactivatable diazirine-AHL was labelled with deuterium and tritium by a postsynthetic catalytic exchange of the hydrogen with its isotopes, using deuterium or tritium labelled water along with catalytic amounts of metal salts under mild basic conditions. The N-(3-oxo-5-diazirinedodecanoyl-[2-3H2])-L-homoserine lactone was successfully synthesized in five steps. Due to a photoactivatable diazirine group and easily tracked radioactive label, the product could be applied in research on the mechanism of inter-kingdom signalling. Importantly, incorporation of the tritium label takes place in the last step of the synthesis. Copyright
Synthesis of Tritium Labelled and Photoactivatable N-Acyl- L -homoserine Lactones: Inter-Kingdom Signalling Molecules
Jakubczyk, Dorota,Brenner-Weiss, Gerald,Br?se, Stefan
, p. 592 - 597 (2015/10/05)
N-Acyl-L-homoserine lactones (AHLs) are signal molecules that are synthesized in nature by Gram-negative bacteria. They allow communication between bacteria (quorum sensing) and between microorganisms and their eukaryotic host cells (inter-kingdom signalling). However, very little is known about the mechanisms of the latter system. Therefore, tritium labelled photoactivatable AHLs were synthesized to identify specific receptors in immune cells (e.g., human polymorphonuclear neutrophils, PMN) that bind to AHL. A photoaffinity label - a diazirine group - was chosen as the smallest possible photoactivatable group that can be activated by light irradiation. The resulting highly active carbene will bind covalently to the closest chemical structure in the pocket of the receptor. The diazirine label was introduced into the AHL molecule according to a literature method. To isolate the labelled receptor from the cellular protein moiety, the AHL was additionally labelled with tritium. During the development of an effective isotopic labelling method, a simple route to hydrogen isotope incorporation into the AHLs was proposed and explored in detail. According to the new protocol, the photoactivatable diazirine-AHL was labelled with deuterium and tritium by a postsynthetic catalytic exchange of the hydrogen with its isotopes, using deuterium or tritium labelled water along with catalytic amounts of metal salts under mild basic conditions.
From in vitro to in cellulo: Structure-activity relationship of (2-nitrophenyl)methanol derivatives as inhibitors of PqsD in Pseudomonas aeruginosa
Storz, Michael P.,Allegretta, Giuseppe,Kirsch, Benjamin,Empting, Martin,Hartmann, Rolf W.
supporting information, p. 6094 - 6104 (2014/08/05)
Recent studies have shown that compounds based on a (2-nitrophenyl)methanol scaffold are promising inhibitors of PqsD, a key enzyme of signal molecule biosynthesis in the cell-to-cell communication of Pseudomonas aeruginosa. The most promising molecule displayed anti-biofilm activity and a tight-binding mode of action. Herein, we report on the convenient synthesis and biochemical evaluation of a comprehensive series of (2-nitrophenyl)methanol derivatives. The in vitro potency of these inhibitors against recombinant PqsD as well as the effect of selected compounds on the production of the signal molecules HHQ and PQS in P. aeruginosa were examined. The gathered data allowed the establishment of a structure-activity relationship, which was used to design fluorescent inhibitors, and finally, led to the discovery of (2-nitrophenyl)methanol derivatives with improved in cellulo efficacy providing new perspectives towards the application of PqsD inhibitors as anti-infectives. This journal is the Partner Organisations 2014.
Validation of PqsD as an anti-biofilm target in pseudomonas aeruginosa by development of small-molecule inhibitors
Storz, Michael P.,Maurer, Christine K.,Zimmer, Christina,Wagner, Nathalie,Brengel, Christian,De Jong, Johannes C.,Lucas, Simon,Muesken, Mathias,Haeussler, Susanne,Steinbach, Anke,Hartmann, Rolf W.
supporting information, p. 16143 - 16146 (2012/11/07)
2-Heptyl-4-hydroxyquinoline (HHQ) and Pseudomonas quinolone signal (PQS) are involved in the regulation of virulence factor production and biofilm formation in Pseudomonas aeruginosa. PqsD is a key enzyme in the biosynthesis of these signal molecules. Using a ligand-based approach, we have identified the first class of PqsD inhibitors. Simplification and rigidization led to fragments with high ligand efficiencies. These small molecules repress HHQ and PQS production and biofilm formation in P. aeruginosa. This validates PqsD as a target for the development of anti-infectives.
