Browse
Submit Data
Databases
API
Help

Dataset Information

11 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Biological evaluation of new largazole analogues: alteration of macrocyclic scaffold with click chemistry.

ABSTRACT: We report the design, synthesis, and biological evaluation of a new series of largazole analogues in which a 4-methylthiazoline moiety was replaced with a triazole and tetrazole ring, respectively. Compound 7 bearing a tetrazole ring was identified to show much better selectivity for HDAC1 over HDAC9 than largazole (10-fold). This work could serve as a foundation for further exploration of selective HDAC inhibitors using a largazole molecular scaffold.

SUBMITTER: Li X

PROVIDER: S-EPMC4027506 | biostudies-other | 2013 Jan

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Publications

Biological evaluation of new largazole analogues: alteration of macrocyclic scaffold with click chemistry.

Li Xianlin X Tu Zhenchao Z Li Hua H Liu Chunping C Li Zheng Z Sun Qiao Q Yao Yiwu Y Liu Jinsong J Jiang Sheng S

ACS medicinal chemistry letters 20121205 1

We report the design, synthesis, and biological evaluation of a new series of largazole analogues in which a 4-methylthiazoline moiety was replaced with a triazole and tetrazole ring, respectively. Compound 7 bearing a tetrazole ring was identified to show much better selectivity for HDAC1 over HDAC9 than largazole (10-fold). This work could serve as a foundation for further exploration of selective HDAC inhibitors using a largazole molecular scaffold. ...[more]

PMID: 24900575

Similar Datasets

Click chemistry enables comprehensive preclinical evaluation of targeted epigenetic therapies [Click-Seq 2]

Project description:The success of targeted therapies hinges on our ability to understand the molecular and cellular mechanism of action of these agents. Here we modify various BET bromodomain inhibitors, an exemplar novel targeted therapy, to create functionally conserved compounds that are amenable to click-chemistry and can be used as molecular probes in vitro and in vivo. Using click-proteomics and click-sequencing we provide new mechanistic insights to explain the gene regulatory function of BRD4 and the transcriptional changes invoked by BET inhibitors. In mouse models of acute leukaemia, we use high resolution microscopy and flow cytometry to highlight the underappreciated heterogeneity of drug activity within tumour cells located in different tissue compartments. We also demonstrate the differential distribution and effects of the drug in normal and malignant cells in vivo. These data provide critical insights that reveal the cellular and molecular details for the efficacy and limitations of these agents. This study provides a framework for the pre-clinical assessment of other conventional and targeted therapies.

2017-07-13 | GSE88749 | GEO

Click chemistry enables comprehensive preclinical evaluation of targeted epigenetic therapies [Click-Seq 1]

2017-07-13 | GSE88748 | GEO

Click chemistry enables comprehensive preclinical evaluation of targeted epigenetic therapies

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-07-13 | GSE88751 | GEO

Click chemistry to probe Hsp90: Synthesis and evaluation of a series of triazole-containing novobiocin analogues.

Project description:A series of triazole-containing novobiocin analogues has been designed, synthesized and their inhibitory activity determined. These compounds contain a triazole ring in lieu of the amide moiety present in the natural product. The anti-proliferative effects of these compounds were evaluated against two breast cancer cell lines (SKBr-3 and MCF-7), and manifested activities similar to their amide-containing counterparts. In addition, Hsp90-dependent client protein degradation was observed via Western blot analyses, supporting a common mode of Hsp90 inhibition for both structural classes.

| S-EPMC2924929 | biostudies-literature

Synthesis and Biological Evaluation of New (-)-Englerin Analogues.

Project description:We report the synthesis and biological evaluation of a series of (-)-englerin A analogues obtained along our previously reported synthetic route based on a stereoselective gold(I) cycloaddition process. This synthetic route is a convenient platform to access analogues with broad structural diversity and has led us to the discovery of unprecedented and easier-to-synthesize derivatives with an unsaturation in the cyclopentyl ring between C4 and C5. We also introduce novel analogues in which the original isopropyl motif has been substituted with cyclohexyl, phenyl, and cyclopropyl moieties. The high selectivity and growth-inhibitory activity shown by these new derivatives in renal cancer cell lines opens new ways toward the final goal of finding effective drugs for the treatment of renal cell carcinoma (RCC).

| S-EPMC4926265 | biostudies-literature

Click chemistry enables comprehensive preclinical evaluation of targeted epigenetic therapies [RNA-seq]

2017-07-13 | GSE88750 | GEO

Click chemistry enables comprehensive preclinical evaluation of targeted epigenetic therapies [ChIP-seq 2]

2017-07-13 | GSE88747 | GEO

Click chemistry enables comprehensive preclinical evaluation of targeted epigenetic therapies [ChIP-seq 1]

2017-07-13 | GSE88746 | GEO

Unnatural Amino Acid Derivatives through Click Chemistry: Synthesis of Triazolylalanine Analogues.

Project description:A novel tert-butyl 2-(1-oxoisolndolin-2-yl)acetate derivative is selectively alkylated with propargyl bromide in the presence of lithium hexamethyldisilazide. After removal of the tert-butyl protecting group, the resulting N-isoindolinyl (ethynylalanine) derivative is reacted with a series of azides under 'click conditions'. The click reactions afford an array of N-isoindolinyl-1,2,3-triazolylalanine derivatives as the free carboxylic adds. Following esterification, the N-isoindolinone protecting group is then transformed into the more easily removable phthaloyl group by selective oxidation at the benzylic position.

| S-EPMC5997291 | biostudies-literature

Improved synthesis and biological evaluation of chelator-modified ?-MSH analogs prepared by copper-free click chemistry.

Project description:Radionuclide chelators (DOTA, NOTA) functionalized with a monofluorocyclooctyne group were prepared. These materials reacted rapidly and in high yield with a fully deprotected azide-modified peptide via Cu-free click chemistry under mild reaction conditions (aqueous solution, room temperature). The resulting bioconjugates bind with high affinity and specificity to their cell-surface receptor targets in vitro and appear stable to degradation in mouse serum over 3h of incubation at 37°C.

| S-EPMC3171621 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data