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An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
A second generation of benzothiadiazine dioxide (BTD) derivatives was synthesized employing benzylation reactions mainly. The chlorophenylmethyl BTD derivatives showed activity against human cytomegalovirus (HCMV) with IC(50) values ranging from 3 to 10 microM. Their 50% cytotoxic concentrations were often >200 microM to lung fibroblast HEL cell proliferation and between 20 and 35 microM for lymphocyte CME cell growth. When cytotoxicity for cell morphology was considered, the minimum cytotoxic concentration for the different BTD derivatives varied between 5 and 200 microM. Some of the anti-HCMV compounds also showed activity against HIV-1 and HIV-2. The chlorophenylmethyl derivative 21 was active against a variety of HCMV clinical isolates from patients with different clinical manifestations and fully maintained its activity against a ganciclovir-resistant HCMV strain. The dibenzyl BTD derivatives did not inhibit HCMV protease, and preliminary pharmacological experiments revealed that their anti-HCMV action stems from interference with an early stage of the viral replicative cycle.
Following exposure to 9-(2-phosphonylmethoxyethyl)adenine (an inhibitor of the cellular DNA polymerases alpha, delta and epsilon), human erythroleukemia K562, human T-lymphoid CEM and murine leukemia L1210 cells markedly accumulated in the S phase of the cell cycle. In contrast to DNA replication, RNA synthesis (transcription) and protein synthesis (mRNA translation) were not affected by 9-(2-phosphonylmethoxyethyl)-adenine. The ribonucleoside triphosphate pools were slightly elevated, while the intracellular levels of all four deoxyribonucleoside triphosphates were 1.5-4-fold increased in 9-(2-phosphonylmethoxyethyl)adenine-treated K562, CEM and L1210 cells. The effect of 9-(2-phosphonylmethoxyethyl)adenine on de novo (thymidylate synthase-mediated) and salvage (thymidine kinase-mediated) dTTP synthesis was investigated using radio-labelled nucleoside precursors. The amount of thymidylate synthase-derived dTTP in the acid soluble pool was 2-4-fold higher in PMEA-treated than in untreated K562 cells, which is in accord with the 3-4-fold expansion of the global dTTP level in the presence of 9-(2-phosphonylmethoxyethyl)adenine. Strikingly, 2-derived dTTP accumulated to a much higher extent (i.e. 16-40-fold) in the soluble dTTP pool upon 9-(2-phosphonylmethoxyethyl)adenine treatment. In keeping with this finding, a markedly increased thymidine kinase activity could be demonstrated in extracts of 9-(2-phosphonylmethoxyethyl)adenine-treated K562 cell cultures. Also, in the presence of 200 microM 9-(2-phosphonylmethoxyethyl)adenine, 14-fold less thymidylate synthase-derived but only 3-fold less thymidine kinase-derived dTTP was incorporated into the DNA of the K562 cells. These data show that thymidine incorporation may be inappropriate as a cell proliferation marker in the presence of DNA synthesis inhibitors such as 9-(2-phosphonylmethoxyethyl)adenine. Our findings indicate that 9-(2-phosphonylmethoxyethyl)adenine causes a peculiar pattern of (deoxy)ribonucleotide metabolism deregulation in drug-treated tumor cells, as a result of the metabolic block imposed by the drug on the S phase of the cell cycle.
In this paper, the authors propose an erosion index for wire materials or wire coatings. In sinking EDM research and practice, an erosion index is commonly available. In wire EDM few efforts have been made to identify possible electrode materials from the point of view of cutting speed. The index is based on physical understanding of the process and uses thermal properties of the electrode material, as is the case for the sinking EDM erosion index. The most important materials used as a coating for wire electrodes, like Zn, Cu, W and Mo, are analyzed and the proposed index is in good correlation with experimental cutting data, both from literature reports and own experiments. The theory can also be applied to alloys, such as brass (Cu-Zn) with different amounts of zinc.
