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https://www.readbyqxmd.com/read/27922047/new-arylated-benzo-h-quinolines-induce-anti-cancer-activity-by-oxidative-stress-mediated-dna-damage
#1
Dharmendra K Yadav, Reeta Rai, Naresh Kumar, Surjeet Singh, Sanjeev Misra, Praveen Sharma, Priyanka Shaw, Horacio Pérez-Sánchez, Ricardo L Mancera, Eun Ha Choi, Mi-Hyun Kim, Ramendra Pratap
The anti-cancer activity of the benzo[h]quinolines was evaluated on cultured human skin cancer (G361), lung cancer (H460), breast cancer (MCF7) and colon cancer (HCT116) cell lines. The inhibitory effect of these compounds on the cell growth was determined by the MTT assay. The compounds 3e, 3f, 3h and 3j showed potential cytotoxicity against these human cancer cell lines. Effect of active compounds on DNA oxidation and expression of apoptosis related gene was studied. We also developed a quantitative method to measure the activity of cyclin-dependent kinases-2 (CDK2) by western blotting in the presence of active compound...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27920924/crystal-structure-of-6-p-tol-yl-benzo-b-naphtho-2-3-d-thio-phene-and-of-an-ortho-rhom-bic-polymorph-of-7-phenyl-anthra-2-3-b-benzo-d-thio-phene
#2
S Gopinath, K Sethusankar, Helen Stoeckli-Evans, Muhamad Rafiq, Arasambattu K Mohanakrishnan
The title compounds, C23H16S, (I), and C26H16S, (II), are benzo-thio-phene derivatives in which the benzo-thio-phene moiety is fused with a naphthalene ring system in (I), and with an anthracene ring system in (II). In (I), the mean plane of the benzo-thio-phene ring system makes a dihedral angle of 2.28 (6)° with the naphthalene ring system, and a dihedral angle of 1.28 (6)° with the anthracene ring system in (II), showing that the fused units are essentially planar. In (I), the 4-methyl-benzene ring substituent makes a dihedral angle of 71...
September 1, 2016: Acta Crystallographica. Section E, Crystallographic Communications
https://www.readbyqxmd.com/read/27919155/-possible-health-risks-from-asbestos-in-drinking-water
#3
Agostino Di Ciaula, Valerio Gennaro
The recent finding of asbestos fibres in drinking water (up to 700.000 fibres/litres) in Tuscany (Central Italy) leads to concerns about health risks in exposed communities. Exposure to asbestos has been linked with cancer at several levels of the gastrointestinal tract, and it has been documented, in an animal model, a direct cytotoxic effect of asbestos fibres on the ileum. It has been recently described a possible link between asbestos and intrahepatic cholangiocarcinoma, and asbestos fibres have been detected in humans in histological samples from colon cancer and in gallbladder bile...
November 2016: Epidemiologia e Prevenzione
https://www.readbyqxmd.com/read/27918994/importance-of-5-6-aryl-substitution-on-the-pharmacological-profile-of-4-2-propyl-1h-benzo-d-imidazol-1-yl-methyl-1-1-biphenyl-2-carboxylic-acid-derived-ppar%C3%AE-agonists
#4
Victoria Obermoser, Robert Mauersberger, Daniela Schuster, Monika Czifersky, Marina Lipova, Monika Siegl, Ulrich Kintscher, Ronald Gust
In this structure-activity relationship study, the influence of aryl substituents at position 5 or 6 on the pharmacological profile of the partial PPARγ agonist 4'-((2-propyl-1H-benzo[d]imidazol-1-yl)methyl)-[1,1'-biphenyl]-2-carboxylic acid was investigated. This lead was previously identified as the essential part of telmisartan to induce PPARγ activation. Para-OCH3-phenyl substitution strongly increased potency and efficacy independent of the position. Both compounds represent full agonists because of strong hydrophobic contacts with the amino acid Phe363 in the ligand binding domain...
November 25, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27917502/relationship-between-increasing-concentrations-of-two-carcinogens-and-statistical-image-descriptors-of-foci-morphology-in-the-cell-transformation-assay
#5
Giulia Callegaro, Raffaella Corvi, Susan Salovaara, Chiara Urani, Federico M Stefanini
Cell Transformation Assays (CTAs) have long been proposed for the identification of chemical carcinogenicity potential. The endpoint of these in vitro assays is represented by the phenotypic alterations in cultured cells, which are characterized by the change from the non-transformed to the transformed phenotype. Despite the wide fields of application and the numerous advantages of CTAs, their use in regulatory toxicology has been limited in part due to concerns about the subjective nature of visual scoring, i...
December 5, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27914353/two-liquid-phase-system-a-promising-technique-for-predicting-bioavailability-of-polycyclic-aromatic-hydrocarbons-in-long-term-contaminated-soils
#6
Congying Wang, Ziyu Wang, Zengbo Li, Riaz Ahmad
A two-liquid-phase system (TLPS), which consisted of soil slurry and silicone oil, was employed to extract polycyclic aromatic hydrocarbons (PAHs) in four long-term contaminated soils in order to assess the bioavailability of PAHs. Extraction kinetics of six PAHs viz. phenanthrene, fluoranthene, pyrene, benzo(a)anthracene, benzo(a)pyrene, dibenzo(a,h)anthrancene were selected to investigate as they covered the susceptible and recalcitrant PAHs in soil. A parallel experiments were also carried out on the microbial degradation of these PAHs in soil with and without biostimulation (by adding (NH4)2HPO4)...
November 30, 2016: Chemosphere
https://www.readbyqxmd.com/read/27913846/potent-mutagenicity-of-some-non-planar-tri-and-tetrachlorinated-biphenyls-in-mammalian-cells-human-cyp2e1-being-a-major-activating-enzyme
#7
Yungang Liu, Keqi Hu, Hansi Jia, Guifang Jin, Hansruedi Glatt, Hao Jiang
Polychlorinated biphenyls (PCBs) have been classified as human carcinogens. Mutagenicity of lower chlorinated biphenyls as well as activation of transcription factors by some other congeners may contribute to the carcinogenicity of PCBs. Recently, we reported that human CYP2E1 activates mono- and dichlorobiphenyls to mutagens. However, mutagenicity of other PCBs and the involvement of other CYPs remained unknown. In this study, Chinese hamster V79-derived cell lines genetically engineered for expression of individual human CYP enzymes and a human hepatocyte (L-02) line endogenously expressing various CYPs were used to determine the activities of several tri- and tetrachlorobiphenyls to induce micronuclei and gene mutations...
December 2, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27908386/genetic-polymorphisms-in-19q13-3-genes-associated-with-alteration-of-repair-capacity-to-bpde-dna-adducts-in-primary-cultured-lymphocytes
#8
Mingyang Xiao, Sha Xiao, Tahar van der Straaten, Ping Xue, Guopei Zhang, Xiao Zheng, Qianye Zhang, Yuan Cai, Cuihong Jin, Jinghua Yang, Shengwen Wu, Guolian Zhu, Xiaobo Lu
Benzo[a]pyrene(B[a]P), and its ultimate metabolite Benzo[a]pyrene 7,8-diol 9,10-epoxide (BPDE), are classic DNA damaging carcinogens. DNA damage in cells caused by BPDE is normally repaired by Nucleotide Excision Repair (NER) and Base Excision Repair (BER). Genetic variations in NER and BER can change individual DNA repair capacity to DNA damage induced by BPDE. In the present study we determined the number of in vitro induced BPDE-DNA adducts in lymphocytes, to reflect individual susceptibility to Polycyclic aromatic hydrocarbons (PAHs)-induced carcinogenesis...
December 2016: Mutation Research
https://www.readbyqxmd.com/read/27908385/the-mutagenic-assessment-of-an-electronic-cigarette-and-reference-cigarette-smoke-using-the-ames-assay-in-strains-ta98-and-ta100
#9
D Thorne, I Crooks, M Hollings, A Seymour, C Meredith, M Gaca
Salmonella typhimurium strains TA98 and TA100 were used to assess the mutagenic potential of the aerosol from a commercially available, rechargeable, closed system electronic-cigarette. Results obtained were compared to those for the mainstream smoke from a Kentucky reference (3R4F) cigarette. Two different test matrices were assessed. Aerosol generated from the e-cigarette was trapped on a Cambridge filter pad, eluted in DMSO and compared to cigarette smoke total particulate matter (TPM), which was generated in the same manner for mutagenicity assessment in the Salmonella assay...
December 2016: Mutation Research
https://www.readbyqxmd.com/read/27908382/water-soluble-and-organic-extracts-of-airborne-particulate-matter-induce-micronuclei-in-human-lung-epithelial-a549-cells
#10
Isabel C Palacio, Silvia B M Barros, Deborah A Roubicek
The in vitro genotoxic effects of organic and water-soluble fractions of airborne particulate matter (PM10) with the cytokinesis blocked micronucleus (MN) test in human alveolar carcinoma cells A549 were investigated. Samples were collected in three different sites of São Paulo State, Brazil, and fifteen soluble metals and the sixteen EPÁs priority polycyclic aromatic hydrocarbons (PAH) were chemically determined. PAHs prevailing were fluoranthene and benzo(ghi)perylene. In the water-soluble extracts, highest concentration of metals was found for zinc, iron, and copper in all places of collection...
December 2016: Mutation Research
https://www.readbyqxmd.com/read/27901495/air-pollution-and-dna-methylation-alterations-in-lung-cancer-a-systematic-and-comparative-study
#11
Cheng-Lan Jiang, Shui-Wang He, Yun-Dong Zhang, He-Xian Duan, Tao Huang, Yun-Chao Huang, Gao-Feng Li, Ping Wang, Li-Ju Ma, Guang-Biao Zhou, Yi Cao
The lung cancer incidence in the Xuanwei and neighboring region, Yunnan, China, is among the highest in China and is attributed to severe air pollution with high benzo(a)pyrene levels. We systematically and comparatively analyzed DNA methylation alterations at genome and gene levels in Xuanwei lung cancer tissues and cell lines, as well as benzo(a)pyrene-treated cells and mouse samples. We obtained a comprehensive dataset of genome-wide cytosine-phosphate-guanine island methylation in air pollution-related lung cancer samples...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27901158/a-structural-study-of-alkaline-earth-metal-complexes-with-hybrid-disila-crown-ethers
#12
Fabian Dankert, Kirsten Reuter, Carsten Donsbach, Carsten von Hänisch
Compounds consisting of [M(1,2-disila-[3n]crown-n)](2+) (M = Mg, Ca, Sr, Ba; n = 5, 6) and [Ba(1,2-disila-benzo[18]crown-6)](2+) cations and different anions were obtained by equimolar reaction of the hybrid disila-crown ethers 1,2-disila[15]crown-5 (1), 1,2-disila[18]crown-6 (2) and 1,2-disila-benzo[18]crown-6 (7) with alkaline earth metal salts. Even with strongly coordinating anions such as Br(-) or I(-) stable complexes could be obtained, showing the good coordination ability of these ligands. The structures of all coordination compounds were determined via single crystal X-ray diffraction (XRD)...
November 30, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/27900826/backbone-degradable-polymers-prepared-by-chemical-vapor-deposition
#13
Fan Xie, Xiaopei Deng, Domenic Kratzer, Kenneth C K Cheng, Christian Friedmann, Shuhua Qi, Luis Solorio, Joerg Lahann
Polymers prepared by chemical vapor deposition (CVD) polymerization have found broad acceptance in research and industrial applications. However, their intrinsic lack of degradability has limited wider applicability in many areas, such as biomedical devices or regenerative medicine. Herein, we demonstrate, for the first time, a backbone-degradable polymer directly synthesized via CVD. The CVD co-polymerization of [2.2]para-cyclophanes with cyclic ketene acetals, specifically 5,6-benzo-2-methylene-1,3-dioxepane (BMDO), results in well-defined, hydrolytically degradable polymers, as confirmed by FTIR spectroscopy and ellipsometry...
November 30, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27897349/bulky-ytterbium-formamidinates-stabilise-complexes-with-radical-ligands-and-related-samarium-tetracyclone-chemistry
#14
Peter Courtney Junk, Daniel Werner, Xuefei Zhao, Stephen Best, Laurent Maron, Glen Deacon
Divalent [Yb(DippForm)2(thf)n] (n = 2 (1a), or 1 (1b); DippForm = N,N'-bis(2,6-diisopropylphenyl)formamidinate) complexes were treated with the ketones: 9-fluorenone (fn), or 2,3,4,5-tetraphenylcyclopentadienone (tpc, tetracyclone), giving ketyl† complexes: [Yb(DippForm)2(fn˙-O)(thf)] (2), and [Yb(DippForm)2(tpc˙-O)] (3) respectively. By contrast, when perfluorobenzophenone (pfb) was treated with either 1a or 1b, transitory ketyl formation was followed by rapid decomposition via a C-F activation pathway, giving [YbF(DippForm)2(thf)] (4a) and a highly unusual fluoride/oxide bridged species: [Yb5F6O2(DippForm)5] (4b)...
November 29, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27896883/curcumin-as-a-multifaceted-compound-against-human-papilloma-virus-infection-and-cervical-cancers-a-review-of-chemistry-cellular-molecular-and-preclinical-features
#15
REVIEW
Manouchehr Teymouri, Matteo Pirro, Thomas P Johnston, Amirhosein Sahebkar
Curcumin, the bioactive polyphenolic ingredient of turmeric, has been extensively studied for its effects on human papilloma virus (HPV) infection as well as primary and malignant squamous cervical cancers. HPV infections, especially those related to HPV 16 and 18 types, have been established as the leading cause of cervical cancer; however, there are also additional contributory factors involved in the etiopathogenesis of cervical cancers. Curcumin has emerged as having promising chemopreventive and anticancer effects against both HPV-related and nonrelated cervical cancers...
November 29, 2016: BioFactors
https://www.readbyqxmd.com/read/27896867/collective-syntheses-of-icetexane-natural-products-based-on-biogenetic-hypotheses
#16
Christophe Thommen, Markus Neuburger, Karl Gademann
A divergent synthesis of 10 icetexane natural products based on a proposed biogenetic cationic ring expansion of a reduced carnosic acid derivative is described. Of these icetexanes, (+)-salvicanol, (-)-cyclocoulterone, (-)-coulterone, (-)-obtusinone D, and (-)-obtusinone E have been synthesized for the first time. In addition, the hypothesis for the non-enzymatic biogenesis of benzo[1,3]dioxole natural products has been experimentally investigated. Additional experimental evidence for the abiotic formation of the methylenedioxy unit is provided, as photolysis of the quinone (+)-komaroviquinone resulted in the formation of the [1,3]dioxole-containing natural product (-)-cyclocoulterone and (+)-komarovispirone...
November 29, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27894903/structural-basis-of-accurate-replication-beyond-a-bulky-major-benzo-a-pyrene-adduct-by-human-dna-polymerase-kappa
#17
Vikash Jha, Hong Ling
Human Y-family DNA polymerase kappa (polκ) is specialized to bypass bulky lesions in DNA in an error-free way, thus protecting cells from carcinogenic bulky DNA adducts. Benzo[a]pyrene (BP) is one of the most ubiquitous polycyclic aromatic hydrocarbons and an environmental carcinogen. BP covalently modifies DNA and generates mutagenic, bulky adducts. The major BP adduct formed in cells is 10S (+)-trans-anti-BP-N(2)-dG adduct (BP-dG), which is associated with cancer. The molecular mechanism of how polκ replicates BP-dG accurately is not clear...
November 19, 2016: DNA Repair
https://www.readbyqxmd.com/read/27894870/a-benzo-b-thiophene-based-selective-type-4-s1p-receptor-agonist
#18
Wooyoung Hur, Hugh Rosen, Nathanael S Gray
S1P receptors (S1PR1-5) are a group of GPCRs activated by a high affinity binding with S1P that have important roles in the regulation of the immune system. A potent S1PR agonist FTY720 is an immunomodulator used to treat multiple sclerosis and several 'second generation' drugs are under clinical development. Subtype-selective agonists have been reported for each S1PR isotype, some of which are used as pharmacological tools for functional studies. Here we report the discovery and initial characterization of compound 5c, a benzo[b]thiophene amino carboxylate which exhibits potent and selective agonist activity for S1PR4...
November 18, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27894210/protective-effects-of-lemongrass-essential-oil-against-benzo-a-pyrene-induced-oxidative-stress-and-dna-damage-in-human-embryonic-lung-fibroblast-cells
#19
Jiao Jiang, Henggui Xu, Hetong Wang, Yining Zhang, Ping Ya, Chun Yang, Fasheng Li
Benzo(a)pyrene (BaP) was a well-known environmental pollutant, numerous studies had implicated BaP as a causative agent in human cancer, particularly lung cancer.The lemongrass essential oil (LEO) possessed various pharmacological activities, especially the anti-oxidative stress and cancer prevention. In the current study, human embryonic lung fibroblast (HELF) cells were treated with 25 mM BaP in the absence or presence of 0.5%, 1% or 2.5% LEO and the cell viability and levels of oxidative stress and DNA damage in the cells were then measured...
November 28, 2016: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/27891231/a-pharmacokinetic-evaluation-and-metabolite-identification-of-the-ghb-receptor-antagonist-ncs-382-in-mouse-informs-novel-therapeutic-strategies-for-the-treatment-of-ghb-intoxication
#20
Garrett R Ainslie, K Michael Gibson, Kara R Vogel
Gamma-aminobutyric acid (GABA) is an endogenous inhibitory neurotransmitter and precursor of gamma-hydroxybutyric acid (GHB). NCS-382 (6,7,8,9-tetrahydro-5-hydroxy-5H-benzo-cyclohept-6-ylideneacetic acid), a known GHB receptor antagonist, has shown significant efficacy in a murine model of succinic semialdehyde dehydrogenase deficiency (SSADHD), a heritable neurological disorder featuring chronic elevation of GHB that blocks the final step of GABA degradation. NCS-382 exposures and elimination pathways remain unknown; therefore, the goal of the present work was to obtain in vivo pharmacokinetic data in a murine model and to identify the NCS-382 metabolites formed by mouse and human...
December 2016: Pharmacology Research & Perspectives
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