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991.
Topoisomerase inhibitors have been in use clinically for the treatment of several diseases for decades. Although those enzymes are significant molecular targets in antibacterial and anticancer chemotherapy very little is known about the possibilities to target fungal topoisomerase II (topo II). Raising concern for the fungal infections, lack of effective drugs and a phenomenon of multidrug resistance underlie a strong need to expand the range of therapeutic options. In this review paper, we discussed the usefulness of fungal topo II as a molecular target for new drug discovery. On the basis of previously published data, we described structural and biochemical differences between fungal and human enzymes as well as a molecular basis of differential sensitivity to known anticancer drugs targeting the latter. This review focuses especially on highlighting the differences that may underlie the selectivity of action of new inhibitors. Distinct sites within fungal topo II in comparison with human counterparts are observed and should be further studied to understand the significance of those sites and their possible usage in design of new drugs. 相似文献
992.
量子计算机最令人期待的用途之一,是作为开发新药、催化剂和材料的工具。它可以精确地模拟“化学物质”和“材料”的量子结构以及行为。但是材料科学家和化学家们警告说,量子机器远未能与当今日益强大的经典模拟方法竞争。 相似文献
993.
An Efficient Synthesis of Porphyrins with Different meso Substituents that Avoids Scrambling in Aqueous Media
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Dr. Agnieszka Nowak‐Król Rémi Plamont Dr. Gabriel Canard Judicaelle Andeme Edzang Prof. Dr. Daniel T. Gryko Prof. Dr. Teodor Silviu Balaban 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(4):1488-1498
We have developed new conditions that afford regioisomerically pure trans‐A2B2‐, A3B‐, and trans‐AB2C‐porphyrins bearing aryl and arylethynyl substituents. The porphyrins were prepared by the acid‐catalyzed condensation of dipyrromethanes with aldehydes followed by oxidation with p‐chloranil or 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ). Optimal conditions for the condensation were identified after examining various reaction parameters such as solvent composition, acid concentration, and reaction time. The conditions identified (for aromatic aldehydes: EtOH/H2O 4:1, [DPM]=4 mM , [aldehyde]=4 mM , [HCl]=38 mM , 16 h; for arylethynyl aldehydes: THF/H2O 2:1, [DPM]=13 mM , [aldehyde]=13 mM , [HCl]=150 mM , 3 h) resulted in the formation of porphyrins in yields of 9–38 % without detectable scrambling. This synthesis is compatible with diverse functionalities such as ester or nitrile. In total, 20 new trans‐A2B2‐, A3B‐, and trans‐AB2C‐porphyrins were prepared. The scope and limitations of the two sets of reaction conditions have been explored. The methodological advantage of this approach is its straightforward access to building blocks and the formation of the porphyrin core in higher yields than by any other methodology and by using environmentally benign and nonhazardous chemicals. 相似文献
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Jean-Pierre Gabriel Joseph Hersch 《Zeitschrift für Angewandte Mathematik und Physik (ZAMP)》1971,22(1):210-215
Summary For the first eigenvalue 1 of a vibrating membrane, the «method of one-dimensional auxiliary problems» gave the lower bounds (19). We present here two new interpretations of those bounds, by means of cutting the membrane either into infinitesimal strips or else into infinitesimal quadratic cells, and adding positive or negative elastic support on each side of each cut. 相似文献
1000.
Ernst Lücker Horst K?nig Wolfgang Gabriel Anton Rosopulo 《Fresenius' Journal of Analytical Chemistry》1992,342(12):941-949
Summary The function of solid sampling graphite furnace atomic absorption spectrometry (SS-GFAAS) in the laboratory-internal preparation, production and standardization of several animal tissue reference materials is described. SS-GFAAS is successfully applied in the production of a bovine liver reference material with a low content of Pb and Cd. The lab-internal production of 5 bovine teeth and 2 bovine bone reference materials illustrates some of the basic problems entailed in the analysis of Pb in osseus matrices and in the production of the reference material itself. In the production of muscle tissue reference material focal or generalized calcification is a serious source of endogenous Pb contamination. This is shown, by way of example, in the calcification of the larval states of Taenia saginata (Cysticercus bovis) in the bovine muscle. Finally, as further examples of the application of SS-GFAAS, the lab-internal production of reference material from bovine blood and equine renal cortex is described. 相似文献