Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Metabolic hydroxylations of trans-stilbene.

ABSTRACT: 1. A study was made of the hydroxylation of trans-stilbene in rabbits, guinea pigs and mice, as well as by rabbit liver microsomes. 2. In the rabbit in vivo, trans-stilbene is converted into 4-hydroxy-,4,4'-dihydroxy-,3-hydroxy-4-methoxy-and 4-hydroxy-3-methoxy-stilbene, and hydroxylation plays a more significant role in the metabolism of trans-stilbene than has previously been reported. 3. Investigation of the hydroxylation of 4-hydroxystilbene in the rabbit in vivo demonstrated its ready conversion into 4,4'-dihydroxystilbene and established its intermediacy in the formation of this compound and the methylated analogues of 3,4-dihydroxystilbene. 4. Hydroxylation of trans-stilbene in the guinea pig was found to follow a pattern similar, both qualitatively and quantitatively, to that in the rabbit. 5. Studies in the mouse revealed only limited yields of 4,4'-dihydroxystilbene. 6. Studies of the hydroxylation of trans-stilbene and 4-hydroxystilbene by rabbit liver microsomes located two of the reactions that occur with these compounds in vivo. 7. Work with a solubilized liver-microsomal preparation provided evidence that ;stilbene hydroxylase' activity is not completely lost on solubilization, thus allowing for future microsomal enzyme-isolation studies.

SUBMITTER: Sinsheimer JE

PROVIDER: S-EPMC1187491 | biostudies-other | 1969 Jan

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

trans-3,3',4,5'-Tetra-meth-oxy-stilbene.

Project description:The title compound, C(18)H(20)O(4), was synthesized by a Wittig-Horner reaction of diethyl 3,4-dimeth-oxy-benzyl-phosphate and 3,5-dimeth-oxy-benzaldehyde. In the crystal, the dihedral angle between the two aromatic rings is 2.47 (12)°. All the meth-oxy groups are almost coplanar with the aromatic ring to which they are attached [C-C-O-C torsion angles = -2.8 (3), -5.2 (4), -176.3 (2) and -178.0 (2)°].

| S-EPMC3212342 | biostudies-literature

Cytotoxic, tubulin-interfering and proapoptotic activities of 4'-methylthio-trans-stilbene derivatives, analogues of trans-resveratrol.

Project description:The aim of this study was to evaluate the cytotoxicity of a series of seven 4'-methylthio-trans-stilbene derivatives against cancer cells: MCF7 and A431 in comparison with non-tumorigenic MCF12A and HaCaT cells. The mechanism of anti-proliferative activity of the most cytotoxic trans-resveratrol analogs: 3,4,5-trimethoxy-4'-methylthio-trans-stilbene (3,4,5-MTS) and 2,4,5-trimethoxy-4'-methylthio-trans-stilbene (2,4,5-MTS) was analyzed and compared with the effect of trans-resveratrol. All the compounds that were studied exerted a stronger cytotoxic effect than trans-resveratrol did. MCF7 cells were the most sensitive to the cytotoxic effect of trans-resveratrol analogs with IC50 in the range of 2.1-6.0 µM. Comparing the cytotoxicity of 3,4,5-MTS and 2,4,5-MTS, a significantly higher cytotoxic activity of these compounds against MCF7 versus MCF12A was observed, whereas no significant difference was observed in cytotoxicity against A431 and HaCaT. In the series of 4'-methylthio-trans-stilbenes, 3,4,5-MTS and 2,4,5-MTS were the most promising compounds for further mechanistic studies. The proapoptotic activity of 3,4,5-MTS and 2,4,5-MTS, estimated with the use of annexin-V/propidium iodide assay, was comparable to that of trans-resveratrol. An analysis of cell cycle distribution showed a significant increase in the percentage of apoptotic cells and G2/M phase arrest in MCF7 and A431 as a result of treatment with 3,4,5-MTS, whereas trans-resveratrol tended to increase the percentage of cells in S phase, particularly in epithelial breast cells MCF12A and MCF7. Both trans-stilbene derivatives enhanced potently tubulin polymerization in a dose-dependent manner with sulfur atom participating in the interactions with critical residues of the paclitaxel binding site of ?-tubulin.

| S-EPMC6214853 | biostudies-literature

Resveratrol analogue 4,4'-dihydroxy-trans-stilbene potently inhibits cancer invasion and metastasis.

Project description:We investigated the preventive effects of resveratrol analogue 4,4'-dihydroxy-trans-stilbene (DHS) on cancer invasion and metastasis. Two different in vivo approaches of mouse and zebrafish lung cancer invasion models were employed in our study. The in vitro results showed that DHS displays potent inhibition on anchorage-dependent or -independent cell growth of LLC cells, leading to impairment of the cell cycle progression with reduction of cell numbers arresting at the G1 phase, an evident accumulation of pre-G1 events correlated with apoptotic behaviour. In addition, DHS induces a marked inhibition of LLC cell migration and matrigel invasion. In a murine lung cancer model, tumour volume, cell proliferation, and tumour angiogenesis were significantly inhibited by DHS. Importantly, liver metastatic lesions were significantly reduced in DHS-treated mice. Similarly, DHS significantly inhibits lung cancer cell dissemination, invasion and metastasis in a zebrafish tumour model. These findings demonstrate that DHS could potentially be developed as a novel therapeutic agent for treatment of cancer and metastasis.

| S-EPMC4734289 | biostudies-literature

Ultrafast Photo-ion Probing of the Ring-Opening Process in Trans-Stilbene Oxide.

Project description:The ultrafast photo-induced ring opening of the oxirane derivative trans-stilbene oxide has been studied through the use of ultrafast UV/UV pump-probe spectroscopy by using photo-ion detection. Single- and multiphoton probe paths and final states were identified through comparisons between UV power studies and synchrotron-based vacuum ultraviolet (VUV) single-photon ionization studies. Three major time-dependent features of the parent ion (sub-450 fs decay, (1.5±0.2) ps, and >100 ps) were observed. These decays are discussed in conjunction with the primary ring-opening mechanism of stilbene oxide, which occurs through C-C dissociation in the oxirane ring. The appearance of fragments relating to the masses of dehydrogenated diphenylmethane (167 amu) and dehydrogenated methylbenzene (90 amu) were also investigated. The appearance of the 167 amu fragment could suggest an alternative ultrafast ring-opening pathway via the dissociation of one of the C-O bonds within the oxirane ring.

| S-EPMC8453962 | biostudies-literature

The resveratrol analogue 3,5,3',4',5'-pentahydroxy-trans-stilbene inhibits cell transformation via MEK.

Project description:Resveratrol, present in grapes and red wine, is reported to be a natural chemopreventive agent against cancer. However, the concentrations required to exert these effects may be difficult to achieve by drinking only 1 or 2 glasses of red wine a day. Therefore, developing more potent, nontoxic analogues of resveratrol may provide a feasible means of achieving an effective physiologic concentration. Here we report that the resveratrol analogue, 3,5,3',4',5'-pentahydroxy-trans-stilbene (RSVL2), inhibits 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced neoplastic transformation in JB6 P+ mouse epidermal cells. Further, we identified MEK/ERK signaling as the direct molecular target for the anticancer effects of RSVL2 and demonstrated that RSVL2 inhibited MEK1, but not Raf1 or ERK2 kinase activity. RSVL2 also dose-dependently suppressed MEK1 kinase activity induced by TPA and the inhibition of H-Ras-induced cell transformation was much stronger for RSVL2 than for PD098059 or resveratrol. Both in vitro and ex vivo pull-down assays indicated that RSVL2, but not resveratrol, directly bound with GST-MEK1, but did not compete with ATP for binding. Docking data indicated that the low inhibitory activity of resveratrol might be due to the lack of the hydroxyl group at the meta position of the B ring, thereby preventing resveratrol from forming a hydrogen bond with the backbone amide group of Ser212, which is the key interaction for stabilizing the inactive conformation of the activation loop.

| S-EPMC2606668 | biostudies-literature

Quantification of the resveratrol analogs trans-2,3-dimethoxy-stilbene and trans-3,4-dimethoxystilbene in rat plasma: application to pre-clinical pharmacokinetic studies.

Project description:trans-2,3-Dimethoxystilbene (2,3-DMS) and trans-3,4-dimethoxystilbene (3,4-DMS) are two synthetic resveratrol (trans-3,5,4'-trihydroxystilbene) analogs. In this study, a simple HPLC method was developed and validated to determine 2,3-DMS and 3,4-DMS in rat plasma. Chromatographic separation was obtained with a reversed-phase HPLC column through a 12.5-min gradient delivery of a mixture of acetonitrile and water at the flow rate of 1.5 mL/min at 50 °C. The lower limit of quantification was 10 ng/mL. After successful validation, the pharmacokinetic profiles of 2,3-DMS and 3,4-DMS were subsequently studied in Sprague-Dawley rats. Upon single intravenous administration (4 mg/kg), 2,3-DMS had a medium volume of distribution of the central compartment (Vc = 2.71 ± 0.51 L/kg), quite rapid clearance (Cl = 52.0 ± 7.0 mL/min/kg), moderate mean transit time (MTT0→last = 131.0 ± 4.5 min) but a fairly long terminal elimination half-life (t1/2 λZ = 288.9 ± 92.9 min). Interestingly, 3,4-DMS displayed a pharmacokinetic profile apparently distinct from 2,3-DMS and it had more extensive distribution (Vc = 5.58 ± 1.73 L/kg), faster clearance (Cl = 143.4 ± 40.5 mL/min/kg) and shorter residence (MTT0→last = 61.4 ± 27.1 min). Following single oral administration (10 mg/kg), 2,3-DMS had low and erratic plasma exposure (Cmax = 37.5 ± 23.7 ng/mL) and poor oral bioavailability (2.22% ± 2.13%) while the oral bioavailability of 3,4-DMS was even poorer than 2,3-DMS. Clearly, the location of the methoxy groups had a significant impact on the pharmacokinetics of resveratrol analogs. This study provided useful information for the design of resveratrol derivatives in future study.

| S-EPMC6271088 | biostudies-literature

The one-dimensional polymer poly[[aqua-(2,2'-bipyridine)cadmium(II)]-μ-trans-stilbene-4,4'-dicarboxyl-ato].

Project description:In the title polymer, [Cd(C(16)H(10)O(4))(C(10)H(8)N(2))(H(2)O)](n), the Cd(II) ion is in a strongly distorted octa-hedral geometry, being coordinated by two N atoms from a 2,2'-bipyridine ligand, three carboxylate O atoms from two symmetry-related trans-stilbene-4,4'-dicarboxyl-ate dianions and one water mol-ecule. The stilbene ligand lies on an inversion centre at the midpoint of the central C=C bond. This feature generates the polymeric structure: adjacent Cd(II) ions are bridged by trans-stilbene-4,4'-dicarboxyl-ate dianions, giving rise to a one-dimensional structure. The coordinated water mol-ecule is involved in interchain O-H⋯O hydrogen bonds.

| S-EPMC2915100 | biostudies-literature

Resveratrol analogue 3,4,4'-trihydroxy-trans-stilbene induces apoptosis and autophagy in human non-small-cell lung cancer cells in vitro.

Project description:AimTo investigate the effects of 3,4,4'-trihydroxy-trans-stilbene (3,4,4'-THS), an analogue of resveratrol, on human non-small-cell lung cancer (NSCLC) cells in vitro.MethodsCell viability of NSCLC A549 cells was determined by MTT assay. Cell apoptosis was evaluated using flow cytometry and TUNEL assay. Cell necrosis was evaluated with LDH assay. The expression of apoptosis- or autophagy-associated proteins was measured using Western blotting. The formation of acidic compartments was detected using AO staining, neutral red staining and Lysotracker-Red staining. LC3 punctae were analyzed with fluorescence microscopy.ResultsTreatment with 3,4,4'-THS (10-80 ?mol/L) concentration-dependently inhibited the cell viability. It did not cause cell necrosis, but induced apoptosis accompanied by up-regulation of cleavaged PARP, caspase3/9 and Bax, and by down-regulation of Bcl-2 and surviving. It also increased the formation of acidic compartments, LC3-II accumulation and GFP-LC3 labeled autophagosomes in the cells. It inhibited the mTOR-dependent pathway, but did not impair autophagic flux. 3,4,4'-THS-induced cell death was enhanced by the autophagy inhibitors 3-MA (5 mmol/L) or Wortmannin (2 ?mol/L). Moreover, 3,4,4'-THS treatment elevated the ROS levels in the cells, and co-treatment with 3-MA further elevated the ROS levels. 3,4,4'-THS-induced apoptosis and autophagy in the cells was attenuated by NAC (10 mmol/L)Conclusion:3,4,4'-THS induces both apoptosis and autophagy in NSCLC A549 cells in vitro. Autophagy inhibitors promote 3,4,4'-THS-induced apoptosis of A549 cells, thus combination of 3,4,4'-THS and autophagy inhibitor provides a promising strategy for NSCLC treatment.

| S-EPMC4814205 | biostudies-literature

Identification of a Synthetic Polyhydroxyphenolic Resveratrol Analogue, 3,3',4,4',5,5'-Hexahydroxy-<i>trans</i>-Stilbene with Anti-SARS-CoV-2 Activity.

Project description:The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus has been causing the COVID-19 pandemic since December 2019, with over 600 million infected persons worldwide and over six million deaths. We investigated the anti-viral effects of polyphenolic green tea ingredients and the synthetic resveratrol analogue 3,3',4,4',5,5'-hexahydroxy-trans-stilbene (HHS), a compound with antioxidant, antitumor and anti-HIV properties. In the TCID50 assay, four out of nine green tea constituents showed minor to modest cell protective effects, whereas HHS demonstrated the highest reduction (1103-fold) of the TCID50, indicating pronounced inhibition of virus replication. HHS was also a highly effective inhibitor of SARS-CoV-2 proliferation in VeroE6 cells with an IC50 value of 31.1 µM. HSS also inhibited the binding of the receptor-binding domain (RBD) of the spike protein to the human angiotensin-converting enzyme 2 (ACE2) receptor (RBD-ACE2) binding with 29% at 100 µM and with 9.2% at 50 µM indicating that the SARS-CoV-2 inhibitory effect might at least in part be attributed to the inhibition of virus binding to ACE2. Based on the chemical similarity to other polyphenols, the oral bioavailability of HHS is likely also very low, resulting in blood levels far below the inhibitory concentration of EGCG against SARS-CoV-2 observed in vitro. However, administration of HHS topically as a nose or throat spray would increase concentrations several-fold above the minimal inhibitory concentration (MIC) in the mucosa and might reduce virus load when administered soon after infection. Due to these promising tissue culture results, further preclinical and clinical studies are warranted to develop HHS as an additional treatment option for SARS-CoV-2 infection to complement vaccines, which is and will be the main pillar to combat the COVID-19 pandemic.

| S-EPMC10056577 | biostudies-literature

The trans-stilbene oxide-active glutathione transferase in human mononuclear leucocytes is identical with the hepatic glutathione transferase mu.

Project description:A glutathione transferase from human mononuclear leucocytes with high activity towards trans-stilbene oxide (GT-tSBO) was purified. GT-tSBO is expressed in only about 50% of the individuals studied. As judged from activity measurements, immunological studies and the fact that only those individuals who express glutathione transferase mu have high activity towards trans-stilbene oxide, it is concluded that the hepatic transferase mu is identical with the glutathione transferase (GT-tSBO) in mononuclear leucocytes.

| S-EPMC1148346 | biostudies-other

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