The Rhodadyns,a New Class of Small Molecule Inhibitors of Dynamin GTPase Activity

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玫瑰红银分光光度法测定纳米银胶体溶液中的痕量银

目的:建立纳米银胶体溶液中银的含量测定方法。方法:以浓硝酸作溶剂溶解纳米粒沉淀后,在表面活性剂作用下,与对二甲氨基苄基罗丹宁(玫瑰红银试剂)反应生成橙红色络合物,采用紫外分光光度法,于475nm波长处检测银含量。结果:测得银离子在0.05～1.50mg.L-1范围内,吸光度与浓度呈良好线性关系(r=0.999 9);平均回收率为96.04%(n=9,RSD为1.82%)。结论:上述方法操作简便,便于开展,方法灵敏,适用于测定纳米银胶体溶液中主要成分的含量测定。     

Viral membranes: an emerging antiviral target for enveloped viruses?

Evaluation of: Wolf MC, Freiberg AN, Zhang T et al. A broad-spectrum antiviral targeting entry of enveloped viruses. Proc. Natl Acad. Sci. USA 107, 3157–3162 (2010).

The emergence and re-emergence of viruses and the widespread antiviral resistance calls for the development of a broad-spectrum strategy for viral infection. The article under review describes an approach to achieve this goal by developing an antiviral rhodanine derivative effective against enveloped viruses targeting the viral lipid membrane. By intercalating into the viral membrane, the compound irreversibly inactivates the virions with virucidal effects. Potential toxic effects on hosts could be minimized by continuous regeneration of cellular membranes. The present strategy exploits the therapeutic window that exists between static viral membranes and biogenic cellular membranes and provides a useful guideline for future research endeavors towards broad-spectrum antiviral approaches for enveloped viruses. Developing a formulation that ensures efficient delivery and pharmacokinetic properties while minimizing systemic toxicity on cell membranes remains a challenge. The advantages and disadvantages of a viral membrane-targeting approach for the control of emerging and re-emerging viruses will be discussed.     

培氟沙星C-3甲叉基绕丹宁衍生物的合成及其抗肿瘤活性

为进一步寻找抗肿瘤氟喹诺酮分子的构建策略,用α,β-不饱和酮为抗菌氟喹诺酮C-3羧基的生物电子排体、绕丹宁环为其稠合功能修饰基进而构建了氟喹诺酮C-3甲叉基绕丹宁类1-乙基-6-氟-7-(4-甲基哌嗪-1-基)-3-［3-取代-2-硫代噻唑烷-4-酮-5-叉甲基］-喹啉-4(1H)-酮(6a~6l)目标化合物,其结构经元素分析和光谱数据确证。初步的体外抗细胞增殖活性筛选结果表明,12个新目标化合物对A549、Hep-3B、HL60 3种肿瘤细胞的活性显著高于母体培氟沙星(1),尤其卤代苯基绕丹宁化合物的活性强于其他取代基,对人非小细胞肺肿瘤细胞A549的活性与对照阿霉素相当,且对正常细胞Vero表现出较低细胞毒作用,显示出较好的选择性。为此,甲叉基绕丹宁替代C-3羧基的衍生物有利于提高氟喹诺酮的抗肿瘤活性。     

Synthesis of New N,N’-Bis(5-arylidene-4-oxo-4,5-dihydrothiazolin-2-yl)piperazine Derivatives Under Microwave Irradiation and Preliminary Biological Evaluation

New N,N’-bis(5-arylidene-4-oxo-4,5-dihydrothiazoline-2-yl)diamine derivatives 5 were prepared in two steps from rhodanine and piperazine, or 1,4-bis(3-amino-propyl)piperazine, under microwave reaction conditions with retention of configuration. Some of these compounds were tested for in vitro antiproliferative activities and for their kinase inhibitory potencies towards six kinases (CDK5/p25, GSK3α/β, DYRK1A, DYRK2, CLK1, and CLK2). The compound 5d showed nanomolar activity towards DYRK1A kinase (IC₅₀ = 0.041 μM).     

Rhodanine and thiohydantoin derivatives for detecting tau pathology in Alzheimer's brains

A novel series of rhodanin (RH) and thiohydantoin (TH) derivatives were designed and synthesized for detecting tau pathology in the brains of patients with Alzheimer's disease (AD). In experiments in vitro using tau and β-amyloid (Aβ) aggregates, the TH derivative, TH2, showed high specific binding to tau aggregates. In hippocampal sections obtained from AD patients, TH2 intensely stained neurofibrillary tangles. In experiments using normal mice, [(125)I]TH2 showed good uptake (1.54%ID/g, 2 min postinjection) into and a rapid washout (0.25%ID/g, 60 min postinjection) from the brain. [(123)I]TH2 should be further investigated as a potential imaging agent for detecting tau pathology.