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Angewandte Chemie (International Ed. in... Oct 2019A palladium-catalyzed dearomative syn-1,4-oxyamination protocol using non-activated arenes has been developed. This one-pot procedure utilizes arenophile chemistry, and...
A palladium-catalyzed dearomative syn-1,4-oxyamination protocol using non-activated arenes has been developed. This one-pot procedure utilizes arenophile chemistry, and the corresponding para-cycloadducts are treated with oxygen nucleophiles via formal allylic substitution, providing direct access to syn-1,4-oxyaminated products. The reaction conditions permit a range of arenes, as well as different O-nucleophiles, such as oximes and benzyl alcohols. Moreover, this process was established in an asymmetric fashion, delivering products with high enantioselectivity. The dearomatized products are amenable to a multitude of further derivatizations ranging from olefin chemistry to C-H activation, giving rise to a diverse set of new functionalities. Overall, this dearomative functionalization offers rapid and controlled formation of molecular complexity, enabling straightforward access to functionalized small molecules from simple and readily available arenes.
Topics: Allyl Compounds; Amines; Catalysis; Cycloaddition Reaction; Molecular Structure; Oxygen; Palladium; Stereoisomerism
PubMed: 31482682
DOI: 10.1002/anie.201909838 -
Molecules (Basel, Switzerland) Jul 2020New chrysin-De-allyl-Pac-1 hybrid analogues, tethered with variable heterocyclic systems (-), were rationally designed and synthesized. The target compounds were...
New chrysin-De-allyl-Pac-1 hybrid analogues, tethered with variable heterocyclic systems (-), were rationally designed and synthesized. The target compounds were screened for in vitro antiproliferative efficacy in the triple-negative breast cancer (TNBC) cell line, MDA-MB-231, and normal human mammary epithelial cells (HMECs). Two compounds, and , had the highest efficacy and selectivity towards MDA-MB-231 cells, and thus, were further evaluated by mechanistic experiments. The results indicated that both compounds and induced apoptosis by (1) inducing cell cycle arrest at the G2 phase in MDA-MB-231 cells, and (2) activating the intrinsic apoptotic pathways in a concentration-dependent manner. Physicochemical characterizations of these compounds suggested that they can be further optimized as potential anticancer compounds for TNBC cells. Overall, our results suggest that and could be suitable leads for developing novel compounds to treat TNBC.
Topics: Allyl Compounds; Antineoplastic Agents; Apoptosis; Cell Cycle; Cell Movement; Cell Proliferation; Female; Flavonoids; Humans; Hydrazones; Piperazines; Triple Negative Breast Neoplasms; Tumor Cells, Cultured
PubMed: 32635530
DOI: 10.3390/molecules25133063 -
Environmental and Molecular Mutagenesis Apr 2009Histone deacetylase (HDAC) inhibitors reactivate epigenetically-silenced genes in cancer cells, triggering cell cycle arrest and apoptosis. Recent evidence suggests that... (Review)
Review
Histone deacetylase (HDAC) inhibitors reactivate epigenetically-silenced genes in cancer cells, triggering cell cycle arrest and apoptosis. Recent evidence suggests that dietary constituents can act as HDAC inhibitors, such as the isothiocyanates found in cruciferous vegetables and the allyl compounds present in garlic. Broccoli sprouts are a rich source of sulforaphane (SFN), an isothiocyanate that is metabolized via the mercapturic acid pathway and inhibits HDAC activity in human colon, prostate, and breast cancer cells. In mouse preclinical models, SFN inhibited HDAC activity and induced histone hyperacetylation coincident with tumor suppression. Inhibition of HDAC activity also was observed in circulating peripheral blood mononuclear cells obtained from people who consumed a single serving of broccoli sprouts. Garlic organosulfur compounds can be metabolized to allyl mercaptan (AM), a competitive HDAC inhibitor that induced rapid and sustained histone hyperacetylation in human colon cancer cells. Inhibition of HDAC activity by AM was associated with increased histone acetylation and Sp3 transcription factor binding to the promoter region of the P21WAF1 gene, resulting in elevated p21 protein expression and cell cycle arrest. Collectively, the results from these studies, and others reviewed herein, provide new insights into the relationships between reversible histone modifications, diet, and cancer chemoprevention.
Topics: Allyl Compounds; Animals; Anticarcinogenic Agents; Cell Line, Tumor; Garlic; Histone Deacetylase Inhibitors; Humans; Isothiocyanates; Models, Molecular; Molecular Structure; Neoplasms; Plants, Edible; Protein Binding; Sulfides; Sulfoxides; Thiocyanates
PubMed: 19197985
DOI: 10.1002/em.20454 -
The FEBS Journal Aug 2008Sodium 2-propenyl thiosulfate, a water-soluble organo-sulfane sulfur compound isolated from garlic, induces apoptosis in a number of cancer cells. The molecular...
Sodium 2-propenyl thiosulfate, a water-soluble organo-sulfane sulfur compound isolated from garlic, induces apoptosis in a number of cancer cells. The molecular mechanism of action of sodium 2-propenyl thiosulfate has not been completely clarified. In this work we investigated, by in vivo and in vitro experiments, the effects of this compound on the expression and activity of rhodanese. Rhodanese is a protein belonging to a family of enzymes widely present in all phyla and reputed to play a number of distinct biological roles, such as cyanide detoxification, regeneration of iron-sulfur clusters and metabolism of sulfur sulfane compounds. The cytotoxic effects of sodium 2-propenyl thiosulfate on HuT 78 cells were evaluated by flow cytometry and DNA fragmentation and by monitoring the progressive formation of mobile lipids by NMR spectroscopy. Sodium 2-propenyl thiosulfate was also found to induce inhibition of the sulfurtransferase activity in tumor cells. Interestingly, in vitro experiments using fluorescence spectroscopy, kinetic studies and MS analysis showed that sodium 2-propenyl thiosulfate was able to bind the sulfur-free form of the rhodanese, inhibiting its thiosulfate:cyanide-sulfurtransferase activity by thiolation of the catalytic cysteine. The activity of the enzyme was restored by thioredoxin in a concentration-dependent and time-dependent manner. Our results suggest an important involvement of the essential thioredoxin-thioredoxin reductase system in cancer cell cytotoxicity by organo-sulfane sulfur compounds and highlight the correlation between apoptosis induced by these compounds and the damage to the mitochondrial enzymes involved in the repair of the Fe-S cluster and in the detoxification system.
Topics: Allyl Compounds; Apoptosis; Catalysis; Cell Cycle; Cell Line; Cell Proliferation; Hydrolysis; Lipids; Magnetic Resonance Spectroscopy; Spectrometry, Fluorescence; Sulfuric Acid Esters; Thioredoxins; Thiosulfate Sulfurtransferase
PubMed: 18616471
DOI: 10.1111/j.1742-4658.2008.06535.x -
Environmental Health Perspectives Dec 1977Haloorganic biocides are widely employed as soil fumigants to combat the destructive action of plant parasitic nematodes and fungi. These substances are dehalogenated by...
Haloorganic biocides are widely employed as soil fumigants to combat the destructive action of plant parasitic nematodes and fungi. These substances are dehalogenated by soil organisms, principally species of Pseudomonas and Flavobacteria, to nontoxic metabolities. The paths of metabolism of a vareity of simply alkyl halides are described with emphasis upon the biodehalogenation step.
Topics: 1-Propanol; Allyl Compounds; Animals; Biotransformation; Butanes; Ethylene Dibromide; Hemeproteins; Hydrocarbons, Chlorinated; Hydrocarbons, Halogenated; Hydrolysis; Nematoda; Oxidation-Reduction; Propane; Propanols; Pseudomonas; Soil Microbiology
PubMed: 348458
DOI: 10.1289/ehp.7721279 -
Journal of Nutritional Science and... 2015Lifestyle-related diseases have complex pathogenesis which consists of several different steps. Basic causes of the diseases are attributed to unhealthy lifestyles in... (Review)
Review
Lifestyle-related diseases have complex pathogenesis which consists of several different steps. Basic causes of the diseases are attributed to unhealthy lifestyles in dietary habits, physical activity and suffering stress. The unhealthy lifestyles induce risk factors such as hypertension, dyslipidemia, obesity, and hyperglycemia. These risk factors all promote arteriosclerosis leading to serious vascular complications (i.e., thrombotic diseases), myocardial infarction and cerebral infarction. The total number of deaths from these thrombotic diseases almost equals that from cancer in our country. Cancer is also a typical lifestyle-related disease. Food has three different functions: the primary function is to provide enough nutrients to meet the metabolic requirements. The secondary function is the one relating to food preference. The third function is to control our body functions, which help reduction of the risk of diseases. Some of the compounds derived from food, especially phytochemicals in edible plants, vegetables and herbs, have potent functions to control our body functions and contribute to promoting our health. In this review article, we overview the lifestyle-related diseases and food functions involving prevention and amelioration of the diseases by food components especially from edible plants and vegetables. As an example, we will describe the food function of garlic and the prevention of lifestyle-related diseases by its components. Allyl sulfides are characteristic flavor compounds derived from garlic, and these organosulfur compounds are responsible for the food function of garlic.
Topics: Allyl Compounds; Antioxidants; Cardiovascular Diseases; Garlic; Humans; Life Style; Sulfides; Sulfur Compounds; Vegetables
PubMed: 26598900
DOI: 10.3177/jnsv.61.S83 -
Report on Carcinogens : Carcinogen... 2011
Topics: Allyl Compounds; Animals; Carcinogens; Humans; Neoplasms
PubMed: 21850126
DOI: No ID Found -
International Journal of Molecular... Jul 2017Bioactive dietary agents have been shown to regulate multiple cancer hallmark pathways. Epidemiologic studies have linked consumption of vegetables, such as garlic and... (Review)
Review
Bioactive dietary agents have been shown to regulate multiple cancer hallmark pathways. Epidemiologic studies have linked consumption of vegetables, such as garlic and onions, to decreased incidence of cancer. Diallyl trisulfide (DATS), a bioactive compound derived from vegetables, has been investigated as an anti-cancer and chemopreventive agent. Preclinical studies provide ample evidence that DATS regulates multiple cancer hallmark pathways including cell cycle, apoptosis, angiogenesis, invasion, and metastasis. DATS has been shown to arrest cancer cells at multiple stages of the cell cycle with the G2/M arrest being the most widely reported. Additionally, increased pro-apoptotic capacity as a result of regulating intrinsic and extrinsic apoptotic pathway components has been widely reported following DATS treatment. Invasion, migration, and angiogenesis represent emerging targets of DATS and support its anti-cancer properties. This review summarizes DATS mechanisms of action as an anti-cancer and chemopreventive agent. These studies provide rationale for future investigation into its use as a cancer chemopreventive agent.
Topics: Allium; Allyl Compounds; Animal Experimentation; Animals; Apoptosis; Biosynthetic Pathways; Cell Cycle; Cell Movement; Chemoprevention; Clinical Trials as Topic; Dietary Supplements; Hormones; Humans; Neoplasms; Plant Extracts; Signal Transduction; Sulfides; Treatment Outcome
PubMed: 28788092
DOI: 10.3390/ijms18081645 -
IARC Monographs on the Evaluation of... 1999
Review
Topics: Allyl Compounds; Animals; Carcinogenicity Tests; Carcinogens; Humans; Hydrocarbons, Chlorinated; Insecticides; Mutagenicity Tests; Mutagens; Neoplasms, Experimental; Occupational Exposure
PubMed: 10476369
DOI: No ID Found -
Report on Carcinogens : Carcinogen... 2011
Topics: Allyl Compounds; Animals; Carcinogens; Disinfectants; Environmental Exposure; Government Regulation; Humans; Hydrocarbons, Chlorinated; United States
PubMed: 21852819
DOI: No ID Found