Design, synthesis, and evaluation of bioactive small molecules.
Design, synthesis, and evaluation of bioactive small molecules.
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生物活性小分子的设计、合成和评估。
DOI：
10.1002/tcr.201200016
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Hua,DuyH
中科院分区：
文献类型：
--
作者：
Hua,DuyH
化学家、生物学家和医学家之间的合作研究项目不可避免地产生了许多有用的药物、生物传感器和医疗仪器。有机化学是药物发现和开发的核心。目前有机合成方法的范围允许构建用于药物筛选的无限小有机分子库。在转化研究项目中，我们专注于发现三种主要疾病的先导化合物：阿尔茨海默病（AD），乳腺癌和病毒感染。在AD项目中，我们采用了合理设计的方法，合成了一类新的三环吡喃酮（TP）化合物，可以保护淀粉样前体蛋白（APP）/早老素-1（PS1）小鼠的记忆和运动功能。TP可以通过几种可能的机制保护神经元死亡，包括它们抑制神经元内和细胞外淀粉样蛋白β（Aβ）聚集体形成的能力，增加胆固醇流出，恢复轴突运输，以及增强长时程增强（LTP）和Aβ寡聚体处理后恢复的LTP。我们还合成了一类新的基于取代喹啉的间隙连接增强剂，其在体外和体内对乳腺癌细胞具有有效的抑制活性。尽管有各种抗病毒药物可用，但病毒对现有抗病毒药物的耐药性和各种未充分研究的病毒感染（如诺如病毒和轮状病毒）的出现强调了开发针对此类感染和其他感染的新抗病毒剂的需求。我们的实验室已经承担了这些项目，以发现新的抗病毒抑制剂。对上述项目的讨论可能会为AD、癌症和病毒感染领域候选药物的未来发展提供启示。
Collaborative research projects between chemists, biologists, and medical scientists have inevitably produced many useful drugs, biosensors, and medical instrumentation. Organic chemistry lies at the heart of drug discovery and development. The current range of organic synthetic methodologies allows for the construction of unlimited libraries of small organic molecules for drug screening. In translational research projects, we have focused on the discovery of lead compounds for three major diseases: Alzheimer's disease (AD), breast cancer, and viral infections. In the AD project, we have taken a rational‐design approach and synthesized a new class of tricyclic pyrone (TP) compounds that preserve memory and motor functions in amyloid precursor protein (APP)/presenilin‐1 (PS1) mice. TPs could protect neuronal death through several possible mechanisms, including their ability to inhibit the formation of both intraneuronal and extracellular amyloid β (Aβ) aggregates, to increase cholesterol efflux, to restore axonal trafficking, and to enhance long‐term potentiation (LTP) and restored LTP following treatment with Aβ oligomers. We have also synthesized a new class of gap‐junction enhancers, based on substituted quinolines, that possess potent inhibitory activities against breast‐cancer cells in vitro and in vivo. Although various antiviral drugs are available, the emergence of viral resistance to existing antiviral drugs and various understudied viral infections, such as norovirus and rotavirus, emphasizes the demand for the development of new antiviral agents against such infections and others. Our laboratories have undertaken these projects for the discovery of new antiviral inhibitors. The discussion of these aforementioned projects may shed light on the future development of drug candidates in the fields of AD, cancer, and viral infections.
一系列新型单阳离子2-芳基/杂芳基取代的6-(2-咪唑啉基)苯并噻唑甲磺酸盐的环保合成、体外抗增殖评估和3D-QSAR分析
影响因子：
3.8
作者：
L. Racané;Lucija Ptiček;Mirela Sedić;Petra Grbčić;Sandra Kraljević Pavelić;B. Bertoša;Irena Sović;G. Karminski
通讯作者：
G. Karminski
影响因子：
6.7
作者：
Racane, Livio;Pavelic, Sandra Kraljevic;Karminski-Zamola, Grace
通讯作者：
Karminski-Zamola, Grace