Browse
Submit Data
Databases
API
Help

Dataset Information

28 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Structure-Activity Relationships of Baicalein and its Analogs as Novel TSLP Inhibitors.

ABSTRACT: Thymic stromal lymphopoietin (TSLP) plays an important role in the differentiation and proliferation of Th2 cells, resulting in eosinophilic inflammation and numerous allergic diseases. Baicalein (1), a major component of Scutellaria baicalensis, was found to be the first small molecule to block TSLP signaling pathways. It inhibited effectively eosinophil infiltration in house dust mite-induced and ovalbumin-challenged mouse models. Structure-activity relationship studies identified compound 11a, a biphenyl flavanone analog, as a novel human TSLP inhibitor for the discovery and development of new anti-allergic drugs.

SUBMITTER: Park BB

PROVIDER: S-EPMC6584507 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Structure-Activity Relationships of Baicalein and its Analogs as Novel TSLP Inhibitors.

Park Bernie Byunghoon BB Choi Jae Wan JW Park Dawon D Choi Doyoung D Paek Jiwon J Kim Hyun Jung HJ Son Se-Young SY Mushtaq Ameeq Ul AU Shin Hyeji H Kim Sang Hoon SH Zhou Yuanyuan Y Lim Taehyeong T Park Ji Young JY Baek Ji-Young JY Kim Kyul K Kwon Hongmok H Son Sang-Hyun SH Chung Ka Young KY Jeong Hyun-Ja HJ Kim Hyung-Min HM Jung Yong Woo YW Lee Kiho K Lee Ki Yong KY Byun Youngjoo Y Jeon Young Ho YH

Scientific reports 20190619 1

Thymic stromal lymphopoietin (TSLP) plays an important role in the differentiation and proliferation of Th2 cells, resulting in eosinophilic inflammation and numerous allergic diseases. Baicalein (1), a major component of Scutellaria baicalensis, was found to be the first small molecule to block TSLP signaling pathways. It inhibited effectively eosinophil infiltration in house dust mite-induced and ovalbumin-challenged mouse models. Structure-activity relationship studies identified compound 11a ...[more]

PMID: 31217492

Similar Datasets

Author Correction: Structure-Activity Relationships of Baicalein and its Analogs as Novel TSLP Inhibitors.

Project description:An amendment to this paper has been published and can be accessed via a link at the top of the paper.

| S-EPMC6985264 | biostudies-literature

Synthesis, Insecticidal, Fungicidal Activities and Structure?Activity Relationships of Tschimganin Analogs.

Project description:For the first time, a novel series of tschimganin analogs were designed, synthesized, and evaluated for their insecticidal and fungicidal activities. Their structures were characterized by ¹H-NMR, 13C-NMR and HRMS. Some of these compounds displayed excellent insecticidal and fungicidal activities, suggesting that they have potential to be used as bifunctional agrochemicals. Compound 3d and 3g with electron donating groups showed better inhibitory activity and growth inhibition activity towards Helicoverpa armigera (Hübner). The properties and positions of the substituents on the benzene ring have an important influence on the acaricidal activity of tschimganin analogs. Topomer comparative molecular field analysis (CoMFA) was employed to develop a three-dimensional quantitative structure-activity relationship model for the compounds against Tetranychus turkestani Ugarov et Nikolski. It was indicated that higher electronegativity was beneficial for acaricidal activity. Moreover, compound 3r having a 2-hydroxy-3,5- dinitrophenyl moiety displayed a fungicidal spectrum as broad as azoxystrobin against these phytopathogens.

| S-EPMC6099738 | biostudies-literature

Structure-activity relationships of novel salicylaldehyde isonicotinoyl hydrazone (SIH) analogs: iron chelation, anti-oxidant and cytotoxic properties.

Project description:Salicylaldehyde isonicotinoyl hydrazone (SIH) is a lipophilic, tridentate iron chelator with marked anti-oxidant and modest cytotoxic activity against neoplastic cells. However, it has poor stability in an aqueous environment due to the rapid hydrolysis of its hydrazone bond. In this study, we synthesized a series of new SIH analogs (based on previously described aromatic ketones with improved hydrolytic stability). Their structure-activity relationships were assessed with respect to their stability in plasma, iron chelation efficacy, redox effects and cytotoxic activity against MCF-7 breast adenocarcinoma cells. Furthermore, studies assessed the cytotoxicity of these chelators and their ability to afford protection against hydrogen peroxide-induced oxidative injury in H9c2 cardiomyoblasts. The ligands with a reduced hydrazone bond, or the presence of bulky alkyl substituents near the hydrazone bond, showed severely limited biological activity. The introduction of a bromine substituent increased ligand-induced cytotoxicity to both cancer cells and H9c2 cardiomyoblasts. A similar effect was observed when the phenolic ring was exchanged with pyridine (i.e., changing the ligating site from O, N, O to N, N, O), which led to pro-oxidative effects. In contrast, compounds with long, flexible alkyl chains adjacent to the hydrazone bond exhibited specific cytotoxic effects against MCF-7 breast adenocarcinoma cells and low toxicity against H9c2 cardiomyoblasts. Hence, this study highlights important structure-activity relationships and provides insight into the further development of aroylhydrazone iron chelators with more potent and selective anti-neoplastic effects.

| S-EPMC4231169 | biostudies-literature

The Anthelmintic Activity of Praziquantel Analogs Correlates with Structure-Activity Relationships at TRPMPZQ Orthologs.

Project description:The anthelmintic drug praziquantel remains a key clinical therapy for treating various diseases caused by parasitic flatworms. The parasite target of praziquantel has remained undefined despite longstanding usage in the clinic, although a candidate ion channel target, named TRPMPZQ, has recently been identified. Intriguingly, certain praziquantel derivatives show different activities against different parasites: for example, some praziquantel analogs are considerably more active against cestodes than against schistosomes. Here we interrogate whether the different activities of praziquantel analogs against different parasites are also reflected by unique structure-activity relationships at the TRPMPZQ channels found in these different organisms. To do this, several praziquantel analogs were synthesized and functionally profiled against schistosome and cestode TRPMPZQ channels. Data demonstrate that structure-activity relationships are closely mirrored between parasites and their TRPMPZQ orthologs, providing further support for TRPMPZQ as the therapeutically relevant target of praziquantel.

| S-EPMC10641913 | biostudies-literature

Structure-Activity Relationship Studies with Tetrahydroquinoline Analogs as EPAC Inhibitors.

Project description:EPAC proteins are therapeutic targets for the potential treatment of cardiac hypertrophy and cancer metastasis. Several laboratories use a tetrahydroquinoline analog, CE3F4, to dissect the role of EPAC1 in various disease states. Here, we report SAR studies with tetrahydroquinoline analogs that explore various functional groups. The most potent EPAC inhibitor 12a exists as a mixture of inseparable E (major) and Z (minor) rotamers. The rotation about the N-formyl group indeed impacts the activity against EPAC.

| S-EPMC5774307 | biostudies-literature

Synthesis, Structure-Activity Relationships, and Antiviral Profiling of 1-Heteroaryl-2-Alkoxyphenyl Analogs as Inhibitors of SARS-CoV-2 Replication.

Project description:The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has led to a pandemic, that continues to be a huge public health burden. Despite the availability of vaccines, there is still a need for small-molecule antiviral drugs. In an effort to identify novel and drug-like hit matter that can be used for subsequent hit-to-lead optimization campaigns, we conducted a high-throughput screening of a 160 K compound library against SARS-CoV-2, yielding a 1-heteroaryl-2-alkoxyphenyl analog as a promising hit. Antiviral profiling revealed this compound was active against various beta-coronaviruses and preliminary mode-of-action experiments demonstrated that it interfered with viral entry. A systematic structure-activity relationship (SAR) study demonstrated that a 3- or 4-pyridyl moiety on the oxadiazole moiety is optimal, whereas the oxadiazole can be replaced by various other heteroaromatic cycles. In addition, the alkoxy group tolerates some structural diversity.

| S-EPMC8840742 | biostudies-literature

Synthesis and structure–activity relationships of aryl fluorosulfate-based inhibitors as novel antitubercular agents

Project description: Not available

| S-EPMC10808981 | biostudies-literature

Structure-Activity Relationships of Novel Tau Ligands: Passive Fibril Binders and Active Aggregation Inhibitors.

Project description:Intrinsically disordered proteins (IDPs) are core components of many biological processes and are central players in several pathologies. Despite being important drug targets, attempts to design small-molecule ligands that would help understand and attenuate their behavior are frustrated by the structural diversity exhibited by these flexible proteins. To accommodate the dynamic nature of IDPs, we developed a procedure that efficiently identifies active small-molecule ligands for disordered proteins. By exploring the chemical space around these ligands, we refined their effect on aggregation and identified molecular features critical for activity and affinity. Notably, the discovery of this new family of disordered protein ligands was achieved more quickly and with less expense than conventional high-throughput screening (HTS) or docking alone would have allowed. The resulting ligands include tau aggregation inhibitors as well as at least one compound that binds fibrils potently but does not appear to perturb the extent of kinetics of aggregation.

| S-EPMC9381419 | biostudies-literature

Structure-activity relationships of a novel pyranopyridine series of Gram-negative bacterial efflux pump inhibitors.

Project description:Recently we described a novel pyranopyridine inhibitor (MBX2319) of RND-type efflux pumps of the Enterobacteriaceae. MBX2319 (3,3-dimethyl-5-cyano-8-morpholino-6-(phenethylthio)-3,4-dihydro-1H-pyrano[3,4-c]pyridine) is structurally distinct from other known Gram-negative efflux pump inhibitors (EPIs), such as 1-(1-naphthylmethyl)-piperazine (NMP), phenylalanylarginine-?-naphthylamide (PA?N), D13-9001, and the pyridopyrimidine derivatives. Here, we report the synthesis and biological evaluation of 60 new analogs of MBX2319 that were designed to probe the structure activity relationships (SARs) of the pyranopyridine scaffold. The results of these studies produced a molecular activity map of the scaffold, which identifies regions that are critical to efflux inhibitory activities and those that can be modified to improve potency, metabolic stability and solubility. Several compounds, such as 22d-f, 22i and 22k, are significantly more effective than MBX2319 at potentiating the antibacterial activity of levofloxacin and piperacillin against Escherichia coli.

| S-EPMC4398657 | biostudies-literature

Structure-Activity Relationships of ENMs

Project description:Current nano-SARs are often based on univariate assessments and fail to provide tiered views on ENM-induced bio-effects. Here we pioneered a multi-hierarchical nano-SAR assessment for a representative ENM, Fe2O3, by metabolomics and proteomics analyses. The established nano-SAR profile allows visualizing the contributions of 7 basic properties of Fe2O3 to its diverse bio-effects. For instance, while surface reactivity is responsible for Fe2O3-induced cell migration, the inflammatory effects of Fe2O3 are determined by aspect ratio (nanorods) or surface reactivity (nanoplates). These nano-SARs were examined in THP-1 cells and animal lungs, which allowed us to decipher the detailed mechanisms including NLRP3 inflammasome pathway and monocyte chemoattractant protein-1 dependent signaling. This study provides new insights for nano-SARs, which may facilitate the tailored design of ENMs to endow them with desired bio-effects.

2019-11-12 | PXD010614 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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