Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Study on the Anticoagulant or Procoagulant Activities of Type II Phenolic Acid Derivatives.

ABSTRACT: In this study, three type II phenolic acids (caffeic acid, p-hydroxycinnamic acid, and ferulic acid) were used to synthesize a total of 18 phenolic acid derivatives. With molecular docking for molecule design and target protein (factors) screening, in combination with the confirmation of target proteins (factors) by surface plasmon resonance, and the evaluation of haemostatic and anticoagulant activities with five blood assays (plasma recalcification time, prothrombin time, activated partial thromboplastin time, fibrinogen, and thrombin time), the data indicated that caffeic acid derivatives showed certain anticoagulant or procoagulant activities and that two other series contained compounds with the best anticoagulant activities. Using Materials Studio analysis, particular functional groups that affect anticoagulant or procoagulant activities were revealed, and these conclusions can guide the discovery of compounds with better activities.

SUBMITTER: Luo X

PROVIDER: S-EPMC6149684 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Study on the Anticoagulant or Procoagulant Activities of Type II Phenolic Acid Derivatives.

Luo Xuan X Du Chuanrong C Cheng Hui H Chen Jian-Hua JH Lin Cuiwu C

Molecules (Basel, Switzerland) 20171128 12

In this study, three type II phenolic acids (caffeic acid, <i>p</i>-hydroxycinnamic acid, and ferulic acid) were used to synthesize a total of 18 phenolic acid derivatives. With molecular docking for molecule design and target protein (factors) screening, in combination with the confirmation of target proteins (factors) by surface plasmon resonance, and the evaluation of haemostatic and anticoagulant activities with five blood assays (plasma recalcification time, prothrombin time, activated part ...[more]

PMID: 29182552

Similar Datasets

Allosteric networks in thrombin distinguish procoagulant vs. anticoagulant activities.

Project description:The serine protease ?-thrombin is a dual-action protein that mediates the blood-clotting cascade. Thrombin alone is a procoagulant, cleaving fibrinogen to make the fibrin clot, but the thrombin-thrombomodulin (TM) complex initiates the anticoagulant pathway by cleaving protein C. A TM fragment consisting of only the fifth and sixth EGF-like domains (TM56) is sufficient to bind thrombin, but the presence of the fourth EGF-like domain (TM456) is critical to induce the anticoagulant activity of thrombin. Crystallography of the thrombin-TM456 complex revealed no significant structural changes in thrombin, suggesting that TM4 may only provide a scaffold for optimal alignment of protein C for its cleavage by thrombin. However, a variety of experimental data have suggested that the presence of TM4 may affect the dynamic properties of the active site loops. In the present work, we have used both conventional and accelerated molecular dynamics simulation to study the structural dynamic properties of thrombin, thrombin:TM56, and thrombin:TM456 across a broad range of time scales. Two distinct yet interrelated allosteric pathways are identified that mediate both the pro- and anticoagulant activities of thrombin. One allosteric pathway, which is present in both thrombin:TM56 and thrombin:TM456, directly links the TM5 domain to the thrombin active site. The other allosteric pathway, which is only present on slow time scales in the presence of the TM4 domain, involves an extended network of correlated motions linking the TM4 and TM5 domains and the active site loops of thrombin.

| S-EPMC3535651 | biostudies-literature

Amino acid composition of human fibrinogen and anticoagulant derivatives.

Project description:1. The amino acid compositions of human fibrinogen and three intermediate anticoagulant derivatives were determined by column chromatography. The derivatives were isolated by ammonium sulphate fractionation and column electrophoresis from solutions of fibrinogen undergoing spontaneous breakdown. One derivative, isolated as the large electrophoretic peak at the end of the clottable period (100% CP) of the parent fibrinogen solution, was labelled LP(100) and others obtained at twice this period (200% CP) were designated as LP(200) and SP(200) (LP, large peak; SP, small peak). 2. Maximal ;molecular' weights of approx. 294000 for LP(100), 137000 for LP(200) and 37000 for SP(200) were calculated for the protein moieties. At least 265 amino acid residues must have been lost from each fibrinogen molecule during the formation of LP(100), and 1362 during the formation of the other two derivatives. 3. Only one derivative (LP(200)) had a partial specific volume ([unk] 0.725ml./g.) different from that of fibrinogen ([unk] 0.721ml./g.). 4. No significant differences in refractive index at 589mmu were detected. 5. Calculation of the total number of ionizable groups/10(5)g. of each protein moiety showed a preponderance of the following numbers of negative charges: 22 in fibrinogen; 24 in LP(100); 26 in LP(200); 49 in SP(200). The isoionic points were estimated to be approx.+0.03pH unit (for fibrinogen), -0.06pH unit for (LP(100)) and +0.28pH unit (for LP(200)) from the pK of imidazole, and 0.78pH unit above the average pK of aspartyl and glutamyl ions (for SP(200)). These figures agree closely with experimentally determined values of the isoelectric point of fibrinogen and its derivatives.

| S-EPMC1198311 | biostudies-other

Structural properties and anticoagulant/cytotoxic activities of heterochiral enantiomeric thrombin binding aptamer (TBA) derivatives.

Project description:The thrombin binding aptamer (TBA) possesses promising antiproliferative properties. However, its development as an anticancer agent is drastically impaired by its concomitant anticoagulant activity. Therefore, suitable chemical modifications in the TBA sequence would be required in order to preserve its antiproliferative over anticoagulant activity. In this paper, we report structural investigations, based on circular dichroism (CD) and nuclear magnetic resonance spectroscopy (NMR), and biological evaluation of four pairs of enantiomeric heterochiral TBA analogues. The four TBA derivatives of the d-series are composed by d-residues except for one l-thymidine in the small TT loops, while their four enantiomers are composed by l-residues except for one d-thymidine in the same TT loop region. Apart from the left-handedness for the l-series TBA derivatives, CD and NMR measurements have shown that all TBA analogues are able to adopt the antiparallel, monomolecular, 'chair-like' G-quadruplex structure characteristic of the natural D-TBA. However, although all eight TBA derivatives are endowed with remarkable cytotoxic activities against colon and lung cancer cell lines, only TBA derivatives of the l-series show no anticoagulant activity and are considerably resistant in biological environments.

| S-EPMC7736819 | biostudies-literature

Spraying phenolic acid-modifiedchitooligosaccharide derivatives improves anthocyanin accumulation in grape

Project description: Not available

| S-EPMC10534123 | biostudies-literature

Synthesis and Acaricidal Activities of Scopoletin Phenolic Ether Derivatives: QSAR, Molecular Docking Study and in Silico ADME Predictions.

Project description:Thirty phenolic ether derivatives of scopoletin modified at the 7-hydroxy position were synthesized, and their structures were confirmed by IR, ¹H-NMR, 13C-NMR, MS and elemental analysis. Preliminary acaricidal activities of these compounds against female adults of Tetranychus cinnabarinus (Boisduval) were evaluated using the slide-dip method. The results indicated that some of these compounds exhibit more pronounced acaricidal activity than scopoletin, especially compounds 32, 20, 28, 27 and 8 which exhibited about 8.41-, 7.32-, 7.23-, 6.76-, and 6.65-fold higher acaricidal potency. Compound 32 possessed the the most promising acaricidal activity and exhibited about 1.45-fold higher acaricidal potency against T. cinnabarinus than propargite. Statistically significant 2D-QSAR model supports the observed acaricidal activities and reveals that polarizability (HATS5p) was the most important parameter controlling bioactivity. 3D-QSAR (CoMFA: q² = 0.802, r² = 0.993; CoMSIA: q² = 0.735, r² = 0.965) results show that bulky substituents at R₄, R₁, R₂ and R₅ (C₆, C₃, C₄, and C₇) positions, electron positive groups at R₅ (C₇) position, hydrophobic groups at R₁ (C₃) and R₂ (C₄), H-bond donors groups at R₁ (C₃) and R₄ (C₆) will increase their acaricidal activity, which provide a good insight into the molecular features relevant to the acaricidal activity for further designing novel acaricidal agents. Molecular docking demonstrates that these selected derivatives display different bide modes with TcPMCA1 from lead compound and they interact with more key amino acid residues than scopoletin. In silico ADME properties of scopoletin and its phenolic ether derivatives were also analyzed and showed potential to develop as good acaricidal candidates.

| S-EPMC6102537 | biostudies-literature

Urease inhibitory activities of β-boswellic acid derivatives.

Project description:UnlabelledBackground and the purpose of the studyBoswellia carterii have been used in traditional medicine for many years for management different gastrointestinal disorders. In this study, we wish to report urease inhibitory activity of four isolated compound of boswellic acid derivative.Methods4 pentacyclic triterpenoid acids were isolated from Boswellia carterii and identified by NMR and Mass spectroscopic analysis (compounds 1, 3-O-acetyl-9,11-dehydro-β-boswellic acid; 2, 3-O-acetyl-11-hydroxy-β-boswellic acid; 3. 3-O- acetyl-11-keto-β-boswellic acid and 4, 11-keto-β-boswellic acid. Their inhibitory activity on Jack bean urease were evaluated. Docking and pharmacophore analysis using AutoDock 4.2 and Ligandscout 3.03 programs were also performed to explain possible mechanism of interaction between isolated compounds and urease enzyme.ResultsIt was found that compound 1 has the strongest inhibitory activity against Jack bean urease (IC50 = 6.27 ± 0.03 μM), compared with thiourea as a standard inhibitor (IC50 = 21.1 ± 0.3 μM).ConclusionThe inhibition potency is probably due to the formation of appropriate hydrogen bonds and hydrophobic interactions between the investigated compounds and urease enzyme active site and confirms its traditional usage.

| S-EPMC3575251 | biostudies-literature

Studies on type II glycogenosis. Effects of cortisone derivatives on acid -glucosidase.

Project description:Cortisone causes a marked increase in the activity of liver acid alpha-glucosidase 2h after injection into male Wistar rats. Studies on rat liver tissue slices, isolated lysosomes and cultured skin fibroblasts have demonstrated similar elevations of acid alpha-glucosidase activity after incubation with cortisone. Cortisone-treated human liver tissue, obtained by needle biopsy, also shows an increase in acid alpha-glucosidase activity. Neutral alpha-glucosidase activity was not stimulated by cortisone in vivo or in liver slices.

| S-EPMC1176643 | biostudies-other

Cyclohexanone and Phenolic Acid Derivatives from Endophytic Fungus <i>Diaporthe foeniculina</i>.

Project description:Chemical investigation of an endophytic fungus Diaporthe foeniculina SCBG-15, led to the isolation of eight new cyclohexanone derivatives, foeniculins A-H (1-8) and three new phenolic acid derivatives, foeniculins I-K (9-11). Their structures were extensively established on the basis of 1H and 13C NMR spectra together with COSY, HSQC, HMBC, and NOESY experiments. The absolute configurations were confirmed by quantum chemical ECD calculations and single-crystal X-ray diffractions. Moreover, the in vitro cytotoxic and antibacterial activities of isolated compounds 1-11 were also evaluated.

| S-EPMC8440800 | biostudies-literature

Insights into the Discovery of Novel Neuroprotective Agents: A Comparative Study between Sulfanylcinnamic Acid Derivatives and Related Phenolic Analogues.

Project description:Exogenous antioxidants may be beneficial therapeutic tools to tackle the oxidative damage in neurodegenerative diseases by regulation of the redox state that is critical for cell viability and organ function. Inspired by natural plant polyphenols, a series of cinnamic acid-based thiophenolic and phenolic compounds were synthesized and their antioxidant and neuroprotective properties were studied. In general, our results showed that the replacement of the hydroxyl group (OH) by a sulfhydryl group (SH) increased the radical scavenging activity and enhanced the reaction rate with 1,1-diphenyl-2-picrylhydrazyl radical (DPPH•) and galvinoxyl radical (GO•). These results correlated well with the lower oxidation potential (Ep) values of thiophenols. However, a lower peroxyl radical (ROO•) scavenging activity was observed for thiophenols in oxygen radical absorbance capacity (ORAC-FL) assay. Furthermore, the introduction of 5-methoxy and 5-phenyl groups in the aromatic ring of 4-thioferulic acid (TFA) 2 and ferulic acid (FA) 1 did not significantly improve their antioxidant activity, despite the slight decrease of Ep observed for compounds 5, 6, and 9. Concerning cinnamic acid amides, the antioxidant profile was similar to the parent compounds. None of the compounds under study presented significant cytotoxic effects in human differentiated neuroblastoma cells. Thiophenolic amide 3 stands out as the most promising thiophenol-based antioxidant, showing cellular neuroprotective effects against oxidative stress inducers (hydrogen peroxide and iron).

| S-EPMC6930627 | biostudies-literature

Synthesis and antibacterial activities of enamine derivatives of dehydroacetic acid.

Project description:Dehydroacetic acid is a common pyrone derivative used commercially as an antibacterial and antifungal agent. Based on the synthesis of dehydroacetic acid (1) from N-hydroxysuccinimdyl acetoacetate, a novel series of enamine-based derivatives were synthesised in order to improve the antibacterial activity of dehydroacetic acid. The antibacterial activities of the synthesised analogues were evaluated against Escherichia coli and Staphylococcus aureus. Derivative 4d (N-Ph) was identified as the most potent inhibitor of S. aureus growth. Overall, derivative 4b (N-Me) showed the best broad-spectrum activity with five-fold greater minimum inhibitory concentration and 11-fold greater minimum biocidal concentration against E. coli when compared to dehydroacetic acid, in addition to improved antibacterial activity against S. aureus.

| S-EPMC5835058 | 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