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Journal of Biomaterials Science.... Apr 2018Redox-responsive solid lipid microparticles were prepared by an emulsification photo-polymerization method. Octadecyl acrylate (ODA) and a cross-linker (i.e. allyl...
Redox-responsive solid lipid microparticles were prepared by an emulsification photo-polymerization method. Octadecyl acrylate (ODA) and a cross-linker (i.e. allyl disulfide (ADS) and octadiene (ODE)) were dissolved in dichloromethane, it was emulsified in poly(vinyl alcohol) solution, and the resulting O/W emulsion was irradiated with UV light. On the scanning electron microscope micrographs, the microparticles were sphere-like and they were not markedly different from the oil droplets in size. Using the atomic compositions analyzed by energy dispersive X-ray spectroscopy, the ODA to cross-linker molar ratio of ODA/ADS microparticles and ODA/ODE ones were calculated to be 1:0.13 and 1:0.15, respectively. In the FT-IR spectra of the microparticles, the signal of the vinyl group was hardly detected, implying that the monomer and the cross-linkers participated in the photo-polymerization. In differential scanning calorimetry study, ODA/ADS microparticles and ODA/ODE ones exhibited their endothermic peaks around 42.9 and 41.3 °C, respectively, possibly due to the melting of polymeric ODA. Dithiothreitol (DTT, a reducing agent) concentration had little effect on the release degree of dye loaded in ODA/ODE microparticles. Whereas, DTT concentration had a significant effect on the release degree of dye loaded in ODA/ADS microparticles. The release degree at 26 °C was weakly affected by DTT concentration. When the temperature was 37 °C, DTT concentration had a strong effect on the release degree. The disulfide cross-linker (i.e. ADS) can be broken to thiol compounds by the reducing agent, resulting in an increase in the release degree.
Topics: Acrylates; Allyl Compounds; Disulfides; Drug Carriers; Lipids; Microspheres; Oxidation-Reduction
PubMed: 29291676
DOI: 10.1080/09205063.2017.1422854 -
Bioorganic & Medicinal Chemistry Oct 2015A series of novel Diallyl disulfide (DADS) derivatives were designed, synthesized and evaluated as chemical agents, which target and modulate multiple facets of...
Multifunctional novel Diallyl disulfide (DADS) derivatives with β-amyloid-reducing, cholinergic, antioxidant and metal chelating properties for the treatment of Alzheimer's disease.
A series of novel Diallyl disulfide (DADS) derivatives were designed, synthesized and evaluated as chemical agents, which target and modulate multiple facets of Alzheimer's disease (AD). The results showed that the target compounds 5a-l and 7e-m exhibited significant anti-Aβ aggregation activity, considerable acetylcholinesterase (AChE) inhibition, high selectivity towards AChE over butyrylcholinesterase (BuChE), potential antioxidant and metal chelating activities. Specifically, compounds 7k and 7l exhibited highest potency towards self-induced Aβ aggregation (74% and 71.4%, 25 μM) and metal chelating ability. Furthermore, compounds 7k and 7l disaggregated Aβ fibrils generated by Cu(2+)-induced Aβ aggregation by 80.9% and 78.5%, later confirmed by transmission electron microscope (TEM) analysis. Besides, 7k and 7l had the strongest AChE inhibitory activity with IC50 values of 0.056 μM and 0.121 μM, respectively. Furthermore, molecular modelling studies showed that these compounds were capable of binding simultaneously to catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. All the target compounds displayed moderate to excellent antioxidant activity with ORAC-FL values in the range 0.546-5.86Trolox equivalents. In addition, absorption, distribution, metabolism and excretion (ADME) profile and toxicity prediction (TOPKAT) of best compounds 7k and 7l revealed that they have drug like properties and possess very low toxic effects. Collectively, the results strongly support our assertion that these compounds could provide good templates for developing new multifunctional agents for AD treatment.
Topics: Acetylcholinesterase; Allyl Compounds; Alzheimer Disease; Amyloid beta-Peptides; Anhydrides; Antioxidants; Binding Sites; Butyrylcholinesterase; Catalytic Domain; Chelating Agents; Cholinesterase Inhibitors; Copper; Disulfides; Humans; Molecular Docking Simulation; Structure-Activity Relationship
PubMed: 26337018
DOI: 10.1016/j.bmc.2015.08.024 -
Drug Testing and Analysis Jan 2017Many N,N-dialkylated tryptamines show psychoactive properties in humans and the number of derivatives involved in multidisciplinary areas of research has grown over the...
Many N,N-dialkylated tryptamines show psychoactive properties in humans and the number of derivatives involved in multidisciplinary areas of research has grown over the last few decades. Whereas some derivatives form the basis of a range of medicinal products, others are predominantly encountered as recreational drugs, and in some cases, the areas of therapeutic and recreational use can overlap. In recent years, 5-methoxy-N,N-diallyltryptamine (5-MeO-DALT) has appeared as a new psychoactive substance (NPS) and 'research chemical' whereas 4-acetoxy-DALT and the ring-unsubstituted DALT have only been detected very recently. Strategies pursued in the authors' laboratories included the preparation and biological evaluation of previously unreported N,N-diallyltryptamines (DALTs). This report describes the analytical characterization of 17 DALTs. Fifteen DALTs were prepared by a microwave-accelerated Speeter and Anthony procedure following established procedures developed previously in the authors' laboratories. In addition to DALT, the substances included in this study were 2-phenyl-, 4-acetoxy-, 4-hydroxy-, 4,5-ethylenedioxy-, 5-methyl-, 5-methoxy-, 5-methoxy-2-methyl-, 5-ethoxy-, 5-fluoro-, 5-fluoro-2-methyl-, 5-chloro-, 5-bromo-, 5,6-methylenedioxy-, 6-fluoro-, 7-methyl, and 7-ethyl-DALT, respectively. The DALTs were characterized by nuclear magnetic resonance spectroscopy (NMR), gas chromatography (GC) quadrupole and ion trap (EI/CI) mass spectrometry (MS), low and high mass accuracy MS/MS, photodiode array detection, and GC solid-state infrared analysis, respectively. A comprehensive collection of spectral data was obtained that are provided to research communities who face the challenge of encountering newly emerging substances where analytical data are not available. These data are also relevant to researchers who might wish to explore the clinical and non-clinical uses of these substances. Copyright © 2016 John Wiley & Sons, Ltd.
Topics: Allyl Compounds; Chromatography, Gas; Hallucinogens; Illicit Drugs; Magnetic Resonance Spectroscopy; Mass Spectrometry; Psychotropic Drugs; Tryptamines
PubMed: 27100373
DOI: 10.1002/dta.1974 -
Anticancer Research Jun 2023Diallyl trisulfide (DATS) has been shown to prevent and inhibit carcinogenesis in cancer cells. We have previously shown DATS's ability to decrease the percentage of...
BACKGROUND/AIM
Diallyl trisulfide (DATS) has been shown to prevent and inhibit carcinogenesis in cancer cells. We have previously shown DATS's ability to decrease the percentage of viable cells, inhibit cell migration and modulate genes involved in the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B) and mitogen-activated protein kinase (MAPK) signaling.
MATERIALS AND METHODS
This study aimed to compare the efficacy of DATS in tumor necrosis factor alpha (TNF-α) induced MDA-MB-231 and MDA-MB-468 cells and investigate its role in cell-death signaling via cell cycle, flow cytometry, and caspase assay.
RESULTS
DATS exhibit a time-dependent accumulation of G/M phase cells in both cell lines, with higher effects in the MDA-MB-468 for all time points. DATS's ability to decrease the percentage of viable cells in both MDA-MB-231 and MDA-MB-468 cells was shown by a significant but slight increase of early and late apoptosis in the presence of DATS compared to control. Moreover, MDA-MB-468 cells showed more sensitivity to the DATS effect, evidenced by the higher percentage of apoptosis than MDA-MB-231 cells. The caspase studies showed a significant increase in caspase 3 and 8 activity in the presence of DATS, compared to control, in both cell lines. DATS showed no significant increase in caspase 9 activity in both cell lines compared to the control.
CONCLUSION
DATS-induced apoptosis in human breast cancer cells is mediated, at least in part, by cell cycle arrest and caspase activity. These findings provide information for future studies into the role of DATS in TNBC therapy and prevention.
Topics: Humans; Tumor Necrosis Factor-alpha; Triple Negative Breast Neoplasms; Cell Line, Tumor; Sulfides; Apoptosis; Allyl Compounds; Caspases
PubMed: 37247921
DOI: 10.21873/anticanres.16407 -
Journal of the American Chemical Society Mar 2017Experimental mechanistic studies of iridium-catalyzed, enantioselective allylic substitution enabled by (phosphoramidite,olefin) ligands are reported. (η-Allylic...
Experimental mechanistic studies of iridium-catalyzed, enantioselective allylic substitution enabled by (phosphoramidite,olefin) ligands are reported. (η-Allylic alcohol)iridium(I) and (η-allyl)iridium(III) complexes were synthesized and characterized by NMR spectroscopy as well as X-ray crystallography. The substrate complexes are catalytically and kinetically competent to be intermediates in allylic substitutions of branched, racemic allylic alcohols with various nucleophiles. In addition, we have identified an off-cycle pathway involving reversible binding of molecular oxygen to iridium, which contributes to the air tolerance of the catalyst system.
Topics: Alkenes; Allyl Compounds; Catalysis; Crystallography, X-Ray; Iridium; Kinetics; Models, Molecular; Molecular Structure; Organometallic Compounds; Organophosphorus Compounds; Stereoisomerism
PubMed: 28267330
DOI: 10.1021/jacs.6b12421 -
The Journal of Chemical Physics Aug 2014We report magic angle spinning, dynamic nuclear polarization (DNP) experiments at magnetic fields of 9.4 T, 14.1 T, and 18.8 T using the narrow line polarizing agents...
We report magic angle spinning, dynamic nuclear polarization (DNP) experiments at magnetic fields of 9.4 T, 14.1 T, and 18.8 T using the narrow line polarizing agents 1,3-bisdiphenylene-2-phenylallyl (BDPA) dispersed in polystyrene, and sulfonated-BDPA (SA-BDPA) and trityl OX063 in glassy glycerol/water matrices. The (1)H DNP enhancement field profiles of the BDPA radicals exhibit a significant DNP Overhauser effect (OE) as well as a solid effect (SE) despite the fact that these samples are insulating solids. In contrast, trityl exhibits only a SE enhancement. Data suggest that the appearance of the OE is due to rather strong electron-nuclear hyperfine couplings present in BDPA and SA-BDPA, which are absent in trityl and perdeuterated BDPA (d21-BDPA). In addition, and in contrast to other DNP mechanisms such as the solid effect or cross effect, the experimental data suggest that the OE in non-conducting solids scales favorably with magnetic field, increasing in magnitude in going from 5 T, to 9.4 T, to 14.1 T, and to 18.8 T. Simulations using a model two spin system consisting of an electron hyperfine coupled to a (1)H reproduce the essential features of the field profiles and indicate that the OE in these samples originates from the zero and double quantum cross relaxation induced by fluctuating hyperfine interactions between the intramolecular delocalized unpaired electrons and their neighboring nuclei, and that the size of these hyperfine couplings is crucial to the magnitude of the enhancements. Microwave power dependent studies show that the OE saturates at considerably lower power levels than the solid effect in the same samples. Our results provide new insights into the mechanism of the Overhauser effect, and also provide a new approach to perform DNP experiments in chemical, biophysical, and physical systems at high magnetic fields.
Topics: Allyl Compounds; Electrons; Glycerol; Magnetic Fields; Polystyrenes; Water
PubMed: 25134564
DOI: 10.1063/1.4891866 -
Molecular Medicine Reports Dec 2021Cytochrome P450 family 2 subfamily E member 1 (CYP2E1) is a member of the cytochrome P450 enzyme family and catalyzes the metabolism of various substrates. CYP2E1 is... (Comparative Study)
Comparative Study
Cytochrome P450 family 2 subfamily E member 1 (CYP2E1) is a member of the cytochrome P450 enzyme family and catalyzes the metabolism of various substrates. CYP2E1 is upregulated in multiple heart diseases and causes damage mainly via the production of reactive oxygen species (ROS). In mice, increased CYP2E1 expression induces cardiac myocyte apoptosis, and knockdown of endogenous CYP2E1 can attenuate the pathological development of dilated cardiomyopathy (DCM). Nevertheless, targeted inhibition of CYP2E1 via the administration of drugs for the treatment of DCM remains elusive. Therefore, the present study aimed to investigate whether diallyl sulfide (DAS), a competitive inhibitor of CYP2E1, can be used to inhibit the development of the pathological process of DCM and identify its possible mechanism. Here, cTnT transgenic mice, which developed typical DCM phenotypes, were used. Following treatment with DAS for 6 weeks, echocardiography, histological analysis and molecular marker detection were conducted to investigate the DAS‑induced improvement on myocardial function and morphology. Biochemical analysis, western blotting and TUNEL assays were used to detected ROS production and myocyte apoptosis. It was found that DAS improved the typical DCM phenotypes, including chamber dilation, wall thinning, fibrosis, poor myofibril organization and decreased ventricular blood ejection, as determined using echocardiographic and histopathological analyses. Furthermore, the regulatory mechanisms, including inhibition both of the oxidative stress levels and the mitochondria‑dependent apoptosis pathways, were involved in the effects of DAS. In particular, DAS showed advantages in terms of improved chamber dilation and dysfunction in model mice, and the improvement occurred in the early stage of the treatment compared with enalaprilat, an angiotensin‑converting enzyme inhibitor that has been widely used in the clinical treatment of DCM and HF. The current results demonstrated that DAS could protect against DCM via inhibition of oxidative stress and apoptosis. These findings also suggest that inhibition of CYP2E1 may be a valuable therapeutic strategy to control the development of heart diseases, especially those associated with CYP2E1 upregulation. Moreover, the development of DAS analogues with lower cytotoxicity and metabolic rate for CYP2E1 may be beneficial.
Topics: Allyl Compounds; Angiotensin-Converting Enzyme Inhibitors; Animals; Apoptosis; Cardiomyopathy, Dilated; Cardiotonic Agents; Cell Line; Cytochrome P-450 CYP2E1; Disease Models, Animal; Enalaprilat; Female; Male; Mice, Transgenic; Mitochondria; Oxidative Stress; Rats; Sulfides; Troponin T
PubMed: 34651661
DOI: 10.3892/mmr.2021.12492 -
Journal of Toxicology and Environmental... Sep 2020Dillapiole -butyl ether is a substance derived from dillapiole, which exhibits potential insecticidal effects on , the principal vector of the Dengue fever, Zika, and...
Dillapiole -butyl ether is a substance derived from dillapiole, which exhibits potential insecticidal effects on , the principal vector of the Dengue fever, Zika, and Chikungunya viruses, as well as , a vector of Dengue fever. As these mosquitoes are resistant to synthetic insecticides, dillapiole -butyl ether may represent a valuable, plant-based alternative for their control. Dillapiole -butyl ether has insecticidal and genotoxic effects on and , as shown by the reduction in clutch size and egg viability, and increased mortality rates, as well as a high frequency of micronuclei and chromosomal aberrations. However, the potential cytotoxic and genotoxic effects of this substance in mammals are still unknown. In Balb/C mice, structural changes were detected in hepatic, renal, and cardiac tissues, which were directly proportional to the concentration of the dose applied, in both genders. The induction of genotoxic, mutagenic, and cytotoxic effects was also observed at the highest concentrations (150 and 328 mg/kg). Further research will be necessary to better characterize the potential genotoxicity of this substance at lower concentrations, for the evaluation of the potential health risks related to its presence in environmental features, such as drinking water.
Topics: Allyl Compounds; Animals; Cell Survival; DNA Damage; Dioxoles; Dose-Response Relationship, Drug; Female; Heart; Kidney; Liver; Male; Mice; Mice, Inbred BALB C; Mutagenicity Tests; Piper
PubMed: 32787530
DOI: 10.1080/15287394.2020.1804026 -
Organic & Biomolecular Chemistry Aug 2017A 3,4-disubstituted pyrrolidine ring was effectively cyclized through SmI-mediated reductive coupling between allyl chloride and an α,β-unsaturated ester, although...
A 3,4-disubstituted pyrrolidine ring was effectively cyclized through SmI-mediated reductive coupling between allyl chloride and an α,β-unsaturated ester, although little has been reported about SmI-promoted C-C bond formation of an allyl chloride with an α,β-unsaturated ester. Selection of either the 3,4-cis- or 3,4-trans-selective cyclization can be accomplished simply by changing the additives from NiI to HMPA during reductive cyclization conducted in HO-THF. Total synthesis of (-)-kainic acid and (+)-allo-kainic acid, which are pyrrolidine alkaloids used in neuroscience and neuropharmacology as useful molecular probes, was successfully achieved by using the stereo-complementary ring closure reactions promoted by SmI for the construction of the 2,3,4-trisubsituted pyrrolidine scaffold of kainoids.
Topics: Allyl Compounds; Cyclization; Esters; Iodides; Kainic Acid; Oxidation-Reduction; Samarium
PubMed: 28748237
DOI: 10.1039/c7ob01427a -
International Journal of Molecular... Nov 2020This study aimed to examine the effects of diallyl trisulfide (DATS), the most potent polysulfide derived from garlic, on metabolic syndrome and myocardial function in...
This study aimed to examine the effects of diallyl trisulfide (DATS), the most potent polysulfide derived from garlic, on metabolic syndrome and myocardial function in rats with metabolic syndrome (MetS). For that purpose, we used 36 male rats divided into control rats, rats with MetS and MetS rats treated with 40 mg/kg of DATS every second day for 3 weeks. In the first part, we studied the impact of DATS on MetS control and found that DATS significantly raised HS, decreased homocysteine and glucose levels and enhanced lipid and antioxidative, while reducing prooxidative parameters. Additionally, this polysulfide improved cardiac function. In the second part, we investigated the impact of DATS on ex vivo induced ischemia/reperfusion (I/R) heart injury and found that DATS consumption significantly improved cardiodynamic parameters and prevented oxidative and histo-architectural variation in the heart. In addition, DATS significantly increased relative gene expression of eNOS, SOD-1 and -2, Bcl-2 and decreased relative gene expression of NF-κB, IL-17A, Bax, and caspases-3 and -9. Taken together, the data show that DATS can effectively mitigate MetS and have protective effects against ex vivo induced myocardial I/R injury in MetS rat.
Topics: Allyl Compounds; Animals; Blood Glucose; Cardiotonic Agents; Garlic; Gene Expression Regulation; Glucose Tolerance Test; Heart Function Tests; Insulin; Lymph Nodes; Metabolic Syndrome; Myocardium; Oxidation-Reduction; Oxidative Stress; Rats, Wistar; Sulfides
PubMed: 33265949
DOI: 10.3390/ijms21239100