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921.
Martínez González S Hernández AI Varela C Rodríguez-Arístegui S Alvarez RM García AB Lorenzo M Rivero V Oyarzabal J Rabal O Bischoff JR Albarrán M Cebriá A Alfonso P Link W Fominaya J Pastor J 《Bioorganic & medicinal chemistry letters》2012,22(5):1874-1878
Phosphoinositide-3-kinase (PI3K) is an important target for cancer therapeutics due to the deregulation of its signaling pathway in a wide variety of human cancers. We describe herein a novel series of imidazo[1,2-a]pyrazines as PI3K inhibitors. 相似文献
922.
Riad Schulz Thomas Emmrich Heidi Lemmerhirt Ulrike Leffler Kristin Sydow Carsten Hirt Thomas Kiefer Andreas Link Patrick J. Bednarski 《Bioorganic & medicinal chemistry letters》2012,22(21):6712-6715
Cancer cells isolated from two patients with malignant non-Hodgkin B-cell lymphomas that became resistant to chemotherapy during clinical treatment were made ?fourfold resistant in culture to anticancer drugs, that is cisplatin, etoposide, methotrexate and bortezomib. Because most resistant lines showed significantly increased expression of the anti-oxidative enzyme glutathione peroxidase 1 (GPx1), GPx1 was investigated as a target for inhibitor development. Virtual screening of a library of diverse structures by docking them to the active site of the X-ray crystal structure of bovine GPx1 uncovered compounds that might block the enzyme. An enzyme assay confirmed an acylhydrazone heterocycle (3) with GPx inhibitory activity. Combinations of 3 with the anticancer drugs listed above led to reversal of resistance in the lymphoma cell lines. 相似文献
923.
Chosson E Santoro F Rochais C Santos JS Legay R Thoret S Cresteil T Sinicropi MS Besson T Dallemagne P 《Bioorganic & medicinal chemistry》2012,20(8):2614-2623
The synthesis of 7-oxo and 7-hydroxy trifluoroallocolchicinoids was achieved through the intramolecular cyclization of o-phenyl-β-phenylalanines. The resulting compounds were evaluated for their cytotoxic activity against KB cells and their inhibitory effect towards the polymerization of tubulin. The results yielded some potent cytotoxic compounds with correlated partial antitubulin effect. 相似文献
924.
Miroslav Kvasnica Lucie Rarova Jana Oklestkova Milos Budesinsky Ladislav Kohout 《Bioorganic & medicinal chemistry》2012,20(24):6969-6978
Sixteen platinum(II) complexes of estrone and estradiol were synthesized in this work to evaluate their cytotoxic activity against several cancer cell lines including estrogen dependent and independent ones. The synthesis of all the complexes was done in three steps. The reaction of steroids with dibromoalkanes was followed by a reaction of the bromoalkyl steroids with 2-(aminomethyl)pyridine or 2-(2-aminoethyl)pyridine. The last step was a reaction of steroidal diamino ligands with potassium tetrachloroplatinate to obtain the desired platinum(II) complexes. Cytotoxicity assays showed that most of the complexes prepared are active against the cancer cell lines used—CEM, U-2 OS, MCF7, MCF7 AL, MDA-MB-468, BT-474, BT-549, and BJ fibroblasts. The six-membered platinum complexes are more active than five-membered ones. 相似文献
925.
Valovičová Z Mesárošová M Trilecová L Hrubá E Marvanová S Krčmář P Milcová A Schmuczerová J Vondráček J Machala M Topinka J Gábelová A 《Mutation research》2012,743(1-2):91-98
Differences between tissues in the expression of drug-metabolizing enzymes may substantially contribute to tissue-specificity of chemical carcinogens. To verify this hypothesis, the spontaneously immortalized human keratinocytes HaCaT were used, in order to evaluate the genotoxic potential of 7H-dibenzo[c,g]carbazole (DBC), a known hepatocarcinogen and sarcomagen, and its synthetic tissue-specific derivatives, 5,9-dimethyl-DBC (DiMeDBC) and N-methyl-DBC (N-MeDBC), which manifest specific tropism to the liver and skin, respectively. HaCaT cells mainly express cytochrome P4501A1 (CYP1A1), which is involved in metabolism of DBC and N-MeDBC, but not DiMeDBC [10]. Both DBC and the sarcomagen N-MeDBC induced significant levels of DNA strand-breaks, micronuclei, and DNA adducts followed by the phosphorylation of the p53 protein and histone H2AX in HaCaT cells. In contrast, the specific hepatocarcinogen DiMeDBC was devoid of any significant genotoxic activity in this cell line. Our study demonstrates that the absence of drug-metabolizing enzyme(s) involved in DiMeDBC metabolism may contribute substantially to the tissue-specific genotoxicity of this hepatocarcinogen. 相似文献
926.
927.
Jana NR 《Neurochemistry international》2012,60(5):443-447
Protein homeostasis is fundamental in normal cellular function and cell survival. The ubiquitin-proteasome system (UPS) plays a central role in maintaining the protein homeostasis network through selective elimination of misfolded and damaged proteins. Impaired function of UPS is implicated in normal aging process and also in several age-related neurodegenerative disorders that are characterized by increased accumulation oxidatively modified proteins and protein aggregates. Growing literature also indicate the potential role of various ubiquitin protein ligases in the regulation of aging process by enhancing the degradation of either central lifespan regulators or abnormally folded and damaged proteins. This review mainly focuses on our current understanding of the importance of UPS function in the regulation of normal aging process. 相似文献
928.
929.
Jana Krajňáková Karoliina Niemi Dušan Gömöry Hely Häggman 《Plant Cell, Tissue and Organ Culture》2012,109(2):353-361
The effects of ectomycorrhizal (ECM) fungi, including Laccaria
bicolor (Maire) Orton, Laccaria laccata (Scop., Fr.) Berk. and Br., along with two strains of Pisolithus tinctorius (Pers.) Coker and Couch, on the proliferation and subsequent maturation of two embryogenic cell lines of Abies cephalonica Loud., designated lines 6 and 8, were investigated. In the presence of these ECM fungi, the proliferation of both embryogenic
cell lines was inhibited. L. bicolor and P. tinctorius strain 2 resulted in the highest inhibition rates. On the other hand, cultivation of embryogenic cultures along with ECM
fungi, termed a dual culture, increased radial growth of both P. tinctorius strains; whereas, L. bicolor and L. laccata did not grow as well in the presence of embryogenic cell masses. The dual culture during the proliferation period of embryogenic
cells, however, enhanced the subsequent embryo formation and maturation of A. cephalonica; i.e. the capability of embryogenic cell lines to form somatic embryos as well as increasing the mean number of somatic embryos
per 1 g fresh weight of embryogenic cell mass. However, levels of responses were highly dependent on the interaction between
the specific embryogenic cell line and fungal strain. 相似文献
930.
Marek?Pet?ivalskyEmail author Pavla?Vaní?ková Markéta?Ryzí Bo?ena?Navrátilová Jana?Piterková Michaela?Sedlá?ová Lenka?Luhová 《Plant Cell, Tissue and Organ Culture》2012,108(2):237-249
The present study investigated changes in the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS)
in isolated mesophyll protoplasts and cell cultures of the cucumber Cucumis sativus cv. Marketer. Although only a minor increase in the level of nitrogen oxide (NO) was observed during the first 7 days of
culture following protoplast isolation, a substantial accumulation of ROS was detected. Compounds known to modulate endogenous
ROS and RNS levels were employed to study their role in cucumber protoplast regeneration and growth. Supplementing the culture
medium with the NO donors S-nitrosoglutathione and sodium nitroprusside and the ROS scavenger ascorbate significantly increased protoplast viability
and cell density. In contrast, cell density was significantly decreased following the addition of catalase to the medium.
Scavenging of ROS and RNS induced the formation of cucumber microcalli, thus suggesting a differential role of NO in the maintenance
of cell viability and in the control of cell division. Our findings confirm the crucial role of controlled ROS and RNS production
in both protoplast regeneration and cellular growth and differentiation. 相似文献