Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Data for the synthesis of new 4-aryloxy-N-arylanilines as potent succinate-cytochrome c reductase inhibitors.

ABSTRACT: In this data article, we have designed a simple and facile protocol for copper-mediated synthesis of new 4-aryloxy-N-arylanilines under mild reaction conditions. The general information and synthetic procedures of all the target compounds were provided, and they were fully characterized by Nuclear Magnetic Resonance (NMR, including ¹H NMR and ¹³C NMR), melting point measurements, and High-Resolution Mass Spectroscopy (HRMS). Furthermore, the inhibitory activities of these compounds against succinate-cytochrome c reductase (SCR) were evaluated, and the methods and procedures of enzyme inhibition experiments were also recorded in this data article. This article is related to "Synthesis of new 4-aryloxy-N-arylanilines and their inhibitory activities against succinate-cytochrome c reductase" (Cheng et al., 2018) [1].

SUBMITTER: Cheng H

PROVIDER: S-EPMC6223225 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Data for the synthesis of new 4-aryloxy-N-arylanilines as potent succinate-cytochrome c reductase inhibitors.

Cheng Hua H Song Wei W Nie Ren R Wang Yu-Xia YX Li Hui-Lian HL Jiang Xiang-Sheng XS Wu Jun-Jun JJ Chen Cheng C Wu Qiong-You QY

Data in brief 20181024

In this data article, we have designed a simple and facile protocol for copper-mediated synthesis of new 4-aryloxy-N-arylanilines under mild reaction conditions. The general information and synthetic procedures of all the target compounds were provided, and they were fully characterized by Nuclear Magnetic Resonance (NMR, including <sup>1</sup>H NMR and <sup>13</sup>C NMR), melting point measurements, and High-Resolution Mass Spectroscopy (HRMS). Furthermore, the inhibitory activities of these c ...[more]

PMID: 30426039

Similar Datasets

Synthesis and biological evaluation of new piplartine analogues as potent aldose reductase inhibitors (ARIs).

Project description:As a continuation of our efforts directed towards the development of anti-diabetic agents from natural sources, piplartine was isolated from Piper chaba, and was found to inhibit recombinant human ALR2 with an IC(50) of 160 μM. To improve the efficacy, a series of analogues have been synthesized by modification of the styryl/aromatic and heterocyclic ring functionalities of this natural product lead. All the derivatives were tested for their ALR2 inhibitory activity, and results indicated that adducts 3c, 3e and 2j prepared by the Michael addition of piplartine with indole derivatives displayed potent ARI activity, while the other compounds displayed varying degrees of inhibition. The active compounds were also capable of preventing sorbitol accumulation in human red blood cells.

| S-EPMC3857970 | biostudies-literature

Excess no predisposes mitochondrial succinate-cytochrome c reductase to produce hydroxyl radical.

Project description:Mitochondria-derived oxygen-free radical(s) are important mediators of oxidative cellular injury. It is widely hypothesized that excess NO enhances O(2)(•-) generated by mitochondria under certain pathological conditions. In the mitochondrial electron transport chain, succinate-cytochrome c reductase (SCR) catalyzes the electron transfer reaction from succinate to cytochrome c. To gain the insights into the molecular mechanism of how NO overproduction may mediate the oxygen-free radical generation by SCR, we employed isolated SCR, cardiac myoblast H9c2, and endothelial cells to study the interaction of NO with SCR in vitro and ex vivo. Under the conditions of enzyme turnover in the presence of NO donor (DEANO), SCR gained pro-oxidant function for generating hydroxyl radical as detected by EPR spin trapping using DEPMPO. The EPR signal associated with DEPMPO/(•)OH adduct was nearly completely abolished in the presence of catalase or an iron chelator and partially inhibited by SOD, suggesting the involvement of the iron-H(2)O(2)-dependent Fenton reaction or O(2)(•-)-dependent Haber-Weiss mechanism. Direct EPR measurement of SCR at 77K indicated the formation of a nonheme iron-NO complex, implying that electron leakage to molecular oxygen was enhanced at the FAD cofactor, and that excess NO predisposed SCR to produce (•)OH. In H9c2 cells, SCR-dependent oxygen-free radical generation was stimulated by NO released from DEANO or produced by the cells following exposure to hypoxia/reoxygenation. With shear exposure that led to overproduction of NO by the endothelium, SCR-mediated oxygen-free radical production was also detected in cultured vascular endothelial cells.

| S-EPMC3698227 | biostudies-literature

Synthesis of immunogenicity-free RNA circles as potent PKR inhibitors

Project description:Exon(s) back-splicing-generated circular RNAs as a group can suppress the double-stranded RNA (dsRNA)-activated protein kinase R (PKR) in cells. We have sought to synthesize immunogenicity-free, short dsRNA-containing circular RNAs as potent PKR inhibitors. Here, we report that circular RNAs synthesized by permuted td introns from T4 bacteriophage and by Anabeana pre-tRNA group I intron induce an immune response. Mechanistically, autocatalytic splicing introduces extra ~74 nt and ~186 nt fragments (E1+E2+spacer) that form additional stable loop structures that likely provoke innate immune responses in circular RNA products. In contrast, circular RNAs produced by T4 RNA ligase without unwanted fragment exhibit little immunogenicity. Importantly, directly-ligated circular RNAs form short dsRNA-regions exhibit 103~106 fold higher efficiency than the reported chemical compounds C16 and 2-AP in suppressing PKR activation, highlighting the use of circular RNAs as novel inhibitors for PKR over-reaction diseases.

2021-12-23 | GSE183941 | GEO

Design, synthesis, and biological evaluation of potent quinoline and pyrroloquinoline ammosamide analogues as inhibitors of quinone reductase 2.

Project description:A variety of ammosamide B analogues have been synthesized and evaluated as inhibitors of quinone reductase 2 (QR2). The potencies of the resulting series of QR2 inhibitors range from 4.1 to 25,200 nM. The data provide insight into the structural parameters necessary for QR2 inhibitory activity. The natural product ammosamide B proved to be a potent QR2 inhibitor, and the potencies of the analogues generally decreased as their structures became more distinct from that of ammosamide B. Methylation of the 8-amino group of ammosamide B was an exception, resulting in an increase in quinone reductase 2 inhibitory activity from an IC(50) of 61 nM to IC(50) 4.1 nM.

| S-EPMC3262027 | biostudies-literature

Ethynylflavones, highly potent, and selective inhibitors of cytochrome P450 1A1.

Project description:The flavone backbone is a well-known pharmacophore present in a number of substrates and inhibitors of various P450 enzymes. In order to find highly potent and novel P450 family I enzyme inhibitors, an acetylene group was incorporated into six different positions of flavone. The introduction of an acetylene group at certain locations of the flavone backbone lead to time-dependent inhibitors of P450 1A1. 3'-Ethynylflavone, 4'-ethynylflavone, 6-ethynylflavone, and 7-ethynylflavone (KI values of 0.035-0.056 μM) show strong time-dependent inhibition of P450 1A1, while 5-ethynylflavone (KI value of 0.51 μM) is a moderate time-dependent inhibitor of this enzyme. Meanwhile, 4'-ethynylflavone and 6-ethynylflavone are highly selective inhibitors toward this enzyme. Especially, 6-ethynylflavone possesses a Ki value of 0.035 μM for P450 1A1 177- and 15-fold lower than those for P450s 1A2 and 1B1, respectively. The docking postures observed in the computational simulations show that the orientation of the acetylene group determines its capability to react with P450s 1A1 and 1A2. Meanwhile, conformational analysis indicates that the shape of an inhibitor determines its inhibitory selectivity toward these enzymes.

| S-EPMC4137986 | biostudies-literature

Discovery of potent pteridine reductase inhibitors to guide antiparasite drug development.

Project description:Pteridine reductase (PTR1) is essential for salvage of pterins by parasitic trypanosomatids and is a target for the development of improved therapies. To identify inhibitors of Leishmania major and Trypanosoma cruzi PTR1, we combined a rapid-screening strategy using a folate-based library with structure-based design. Assays were carried out against folate-dependent enzymes including PTR1, dihydrofolate reductase (DHFR), and thymidylate synthase. Affinity profiling determined selectivity and specificity of a series of quinoxaline and 2,4-diaminopteridine derivatives, and nine compounds showed greater activity against parasite enzymes compared with human enzymes. Compound 6a displayed a K(i) of 100 nM toward LmPTR1, and the crystal structure of the LmPTR1:NADPH:6a ternary complex revealed a substrate-like binding mode distinct from that previously observed for similar compounds. A second round of design, synthesis, and assay produced a compound (6b) with a significantly improved K(i) (37 nM) against LmPTR1, and the structure of this complex was also determined. Biological evaluation of selected inhibitors was performed against the extracellular forms of T. cruzi and L. major, both wild-type and overexpressing PTR1 lines, as a model for PTR1-driven antifolate drug resistance and the intracellular form of T. cruzi. An additive profile was observed when PTR1 inhibitors were used in combination with known DHFR inhibitors, and a reduction in toxicity of treatment was observed with respect to administration of a DHFR inhibitor alone. The successful combination of antifolates targeting two enzymes indicates high potential for such an approach in the development of previously undescribed antiparasitic drugs.

| S-EPMC2234164 | biostudies-literature

Structure-Based Design and Synthesis of New Estrane-Pyridine Derivatives as Cytochrome P450 (CYP) 1B1 Inhibitors.

Project description:Inhibition of cytochrome P450 (CYP) 1B1 is a promising therapeutic strategy, as such an inhibitor could modulate the bioactivation of procarcinogens while reducing drug resistance. Based on docking studies, the synthesis of 12 estra-1,3,5(10)-triene derivatives containing a pyridin-3-/4-yl moiety at position C2, C3, or C4 was performed, and we measured their inhibitory activity on CYP1B1 using the ethoxyresorufin-O-deethylase (EROD) assay. The position of the nitrogen atom in the aromatic ring has little influence on their inhibition potency, but compounds with a pyridinyl at C2 of the steroid nucleus are more potent CYP1B1 inhibitors than those with a pyridinyl at C3 or C4. Estradiol derivatives (OH at C17?) are also 10-fold more potent inhibitors than estrone derivatives (carbonyl at C17). Thus, 2-(pyridin-3-yl)-estradiol (4a) is the best CYP1B1 inhibitor (IC50 = 0.011 ?M) from this series of compounds, and the best steroid inhibitor reported until now. It is also 7.5-fold more potent than the well-known nonsteroidal CYP1B1 inhibitor ?-naphthoflavone (IC50 = 0.083 ?M).

| S-EPMC5683706 | biostudies-literature

Synthesis of bis(aryloxy)fluoromethanes using a heterodihalocarbene strategy.

Project description:A side-product present in the herbicide pyroxasulfone was synthesized. The construction of a bis(aryloxy)fluoromethane moiety was necessary, for which no existing method was available. We report a simple, new procedure which we applied to the synthesis of some of these unusual structures.

| S-EPMC8056069 | biostudies-literature

Design, Synthesis and Molecular Docking of Novel Acetophenone-1,2,3-Triazoles Containing Compounds as Potent Enoyl-Acyl Carrier Protein Reductase (InhA) Inhibitors.

Project description:New medications are desperately needed to combat rising drug resistance among tuberculosis (TB) patients. New agents should ideally work through unique targets to avoid being hampered by preexisting clinical resistance to existing treatments. The enoyl-acyl carrier protein reductase InhA of M. tuberculosis is one of the most crucial targets since it is a promising target that has undergone extensive research for anti-tuberculosis drug development. A well-known scaffold for a variety of biological activities, including antitubercular activity, is the molecular linkage of a1,2,3-triazole with an acetamide group. As a result, in the current study, which was aided by ligand-based molecular modeling investigations, 1,2,3-triazolesweredesigned and synthesized adopting the CuAAC aided cycloaddition of 1-(4-(prop-2-yn-1-yloxy)phenyl)ethanone with appropriate acetamide azides. Standard spectroscopic methods were used to characterize the newly synthesized compounds. In vitro testing of the proposed compounds against the InhA enzyme was performed. All the synthesized inhibitors completely inhibited the InhA enzyme at a concentration of 10 µM that exceeded Rifampicin in terms of activity. Compounds 9, 10, and 14 were the most promising InhA inhibitors, with IC50 values of 0.005, 0.008, and 0.002 µM, respectively. To promote antitubercular action and investigate the binding manner of the screened compounds with the target InhA enzyme's binding site, a molecular docking study was conducted.

| S-EPMC9316523 | biostudies-literature

WST-assay data reveal a pH dependence of the mitochondrial succinate reductase in osteoblast-like cells.

Project description:The data presented in this article are related to the research article entitled "Increased osteoblast viability at alkaline pH in vitro provides a new perspective on bone regeneration" (doi: 10.1016/j.bbrep.2017.02.001; (Galow et al., 2017) [1]). The water soluble tetrazolium (WST) proliferation assay detects the metabolic activity of the respiratory chain of cultured cells. The assay is based on changes in the light absorbance resulting from the metabolism of WST-1 into formazane by mitochondrial succinate reductase. We present data of three different tests that were carried out to check whether WST assay readouts are pH-dependent. In a first test, a possible pH effect on the photometric measurements, for example by shifting the absorbance spectrum of the pH indicator of the cell culture medium, was excluded. Because the second test revealed a significant pH-dependence of the activity of the mitochondrial succinate reductase, a third long-term test was conducted to analyze possible changes of the pH dependence over time. The higher absorbance per one million cells at alkaline pH, which was approximately four-fold at pH 8.4 compared to the pH-7.4 reference on day one decayed gradually, with the pH-differences equilibrating over six days.

| S-EPMC5426033 | biostudies-literature

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