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排序方式: 共有405条查询结果,搜索用时 0 毫秒
401.
Linfeng Li Adedoyin D. Abraham Qiong Zhou Hadi Ali Jeremy V. O’Brien Brayden D. Hamill John J. Arcaroli Wells A. Messersmith Daniel V. LaBarbera 《Marine drugs》2014,12(9):4833-4850
Recently, we characterized neoamphimedine (neo) as an ATP-competitive inhibitor of the ATPase domain of human Topoisomerase IIα. Thus far, neo is the only pyridoacridine with this mechanism of action. One limiting factor in the development of neo as a therapeutic agent has been access to sufficient amounts of material for biological testing. Although there are two reported syntheses of neo, both require 12 steps with low overall yields (≤6%). In this article, we report an improved total synthesis of neo achieved in 10 steps with a 25% overall yield. In addition, we report an expanded cytotoxicity study using a panel of human cancer cell lines, including: breast, colorectal, lung, and leukemia. Neo displays potent cytotoxicity (nM IC50 values) in all, with significant potency against colorectal cancer (lowest IC50 = 6 nM). We show that neo is cytotoxic not cytostatic, and that neo exerts cytotoxicity by inducing G2-M cell cycle arrest and apoptosis. 相似文献
402.
403.
du Toit N McGorum BC Pemberton AD Brown J Dacre KJ 《Veterinary immunology and immunopathology》2007,115(1-2):35-42
Cyathostomins (Cyathostominae) are regarded as the most pathogenic equine nematode worldwide. These nematodes are difficult to control in equine populations due to emerging anthelmintic resistance and evasion of encysted larval cyathostomins to regular modern anthelmintics. Mast cells and their proteinases have been shown to play a role in the mammalian immune response to nematode infections. Involvement of mast cells and mast cell proteinases in the equine immune response to cyathostomin infection is proposed. A technique was established to perform immunohistochemical staining using polyclonal rabbit anti-equine mast cell proteinase-1 (eqMCP-1) and anti-equine tryptase on formalin-fixed large intestinal sections, from horses classified as cyathostomin positive and negative at the time of death based upon larval enumeration. Quantitative analysis of antibody labelled mast cells was used to detect mast cell proteinases in equine large intestinal sections positive and negative for cyathostomin larvae. This demonstrated an increase in equine tryptase labelled mucosal and submucosal mast cells in cyathostomin positive horses. This study has established an immunohistochemical technique to demonstrate mast cell proteinases in formalin-fixed large intestinal sections. This technique may be used to determine possible involvement of mast cells and their proteinases in the equine immune response to cyathostomin larvae. Further studies are required to define a specific role. 相似文献
404.
Green fluorescent protein (GFP) and its derivatives have transformed the use and analysis of proteins for diverse applications. Like proteins, RNA has complex roles in cellular function and is increasingly used for various applications, but a comparable approach for fluorescently tagging RNA is lacking. Here, we describe the generation of RNA aptamers that bind fluorophores resembling the fluorophore in GFP. These RNA-fluorophore complexes create a palette that spans the visible spectrum. An RNA-fluorophore complex, termed Spinach, resembles enhanced GFP and emits a green fluorescence comparable in brightness with fluorescent proteins. Spinach is markedly resistant to photobleaching, and Spinach fusion RNAs can be imaged in living cells. These RNA mimics of GFP provide an approach for genetic encoding of fluorescent RNAs. 相似文献
405.
Gerstein MB Lu ZJ Van Nostrand EL Cheng C Arshinoff BI Liu T Yip KY Robilotto R Rechtsteiner A Ikegami K Alves P Chateigner A Perry M Morris M Auerbach RK Feng X Leng J Vielle A Niu W Rhrissorrakrai K Agarwal A Alexander RP Barber G Brdlik CM Brennan J Brouillet JJ Carr A Cheung MS Clawson H Contrino S Dannenberg LO Dernburg AF Desai A Dick L Dosé AC Du J Egelhofer T Ercan S Euskirchen G Ewing B Feingold EA Gassmann R Good PJ Green P Gullier F Gutwein M Guyer MS Habegger L Han T Henikoff JG 《Science (New York, N.Y.)》2010,330(6012):1775-1787