A convenient new and efficient commercial synthetic route for dasatinib (Sprycel®)

A new and efficient synthetic route for dual-Src/Abl kinase inhibitor dasatinib (Sprycel®), an anticancer drug, is described. This commercially viable process yields dasatinib monohydrate free of potential impurities with consistent yield of 68% in route A and 61% in route B with HPLC purity >99.80% over four stages.     

Exploring the mechanisms of renoprotection against progressive glomerulosclerosis

In this review, I introduce the strategy developed by our laboratory to explore the mechanisms of renoprotection against progressive glomerulosclerosis leading to renal death. First, I describe the experimental rat model in which disturbances of vascular regeneration and glomerular hemodynamics lead to irreversible glomerulosclerosis. Second, I discuss the possible mechanisms determining the progression of glomerulosclerosis and introduce a new imaging system based on intravital confocal laser scanning microscopy. Third, I provide an in-depth review of the regulatory glomerular hemodynamics at the cellular and molecular levels while focusing on the pivotal role of Ca(2+)-dependent gap junctional intercellular communication in coordinating the behavior of mesangial cells. Last, I show that local delivery of renoprotective agents, in combination with diagnostic imaging of the renal microvasculature, allows the evaluation of the therapeutic effects of angiotensin II receptor and cyclooxygenase activity local blockade on the progression of glomerulosclerosis, which would otherwise lead to renal death.     

Optical probes for detection and quantification of neutrophils’ oxidative burst. A review

Neutrophils, also known as polymorphonuclear leukocytes (PMN), are the most common type of white blood cells, comprising about 50-70% of all white blood cells. In the event of inflammatory processes, neutrophils display increased mobility, tissue influx ability, prolonged life span, and an increased phagocytic capacity, constituting the initial participants in the cellular defense of the organism. One of the most important defense systems of neutrophils corresponds to their ability to mediate a strong oxidative burst through the formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). While oxidative burst is important for the elimination of invading microorganisms, the overproduction of ROS and RNS or the impairment of endogenous antioxidant defenses may result to detrimental effects to the host. The nature and the extent of ROS and RNS production by neutrophils in response to different stimuli is, consequently, a matter of extensive research, with scientific reports showing an enormous variability on the detection methodologies employed. This review attempts to provide a critical assessment of the most common approaches to identify and quantify reactive species formed during the neutrophils’ oxidative burst. The detection mechanisms and performance, as well as advantages and limitations of the different methodologies, are scrutinized, focusing on the use of fluorimetric, chemiluminometric and colorimetric probes.     

离子液体的毒性

离子液体因其特有的物化性质受到越来越多的关注,并被认为是环境友好的"绿色产品"。但是有关离子液体的潜在毒性一直被人们所忽视,直到最近才有少量报道。本文综述了离子液体毒性研究的相关情况：详细介绍了离子液体毒性研究的各种方法及优缺点;离子液体对各类生物的急性毒性和慢性毒性;离子液体的各部分组成,尤其是阳离子核种类、取代烷基碳链长度和阴离子种类对离子液体毒性的影响情况,以及SAR理论在离子液体毒性研究中的应用情况。在此基础上提出今后离子液体毒性研究的发展方向。     

慢性肾衰肾虚证患者血清微量元素的变化及其临床意义探讨

讨论了慢性肾衰肾阳虚和肾阴虚见证者血清微量元素。结果显示：肾阳虚患者血清Ｃｕ、Ｃｕ／Ｚｎ明显高于健康对照组,而血清Ｚｎ和Ｆｅ低于对照组,肾阳虚患者血清Ｃｕ、Ｃｕ／Ｚｎ也明显高于肾阴虚组,而血清Ｚｎ是低的,在肾阴虚组与对照组之间Ｃｕ、Ｚｎ、Ｃｕ／Ｚｎ均无明显差异。     

Biological evaluation of 2-methylpyrimidine derivatives as active pan Bcr-Abl inhibitors

We designed a series of 2-methylpyrimidine derivatives as new BCR-ABL inhibitors using scaffold-hopping strategy.These synthetic compounds exhibited significant inhibition against a broad spectrum of Bcr-Abl mutants including the gatekeeper T315I mutant.Compound 7u showed very potent kinase inhibitory activities against Bcr-Abl WT,Bcr-Abl E255K,Bcr-Abl Q252H,Bcr-Abl G250E and Bcr-Abl T315I,with IC50 values of 0.13 nM,0.17 nM,0.24 nM,0.19 nM and 0.65μM,respectively.This compound also displayed anti-proliferation activity against K562 cell line with an IC50 value of 1.1 nM,thus representing a new lead for further optimization.     

微量元素硒的抗癌作用

对硒在恶性肿瘤的防治及其作用机理进行了总结和讨论,硒通过调节机体免疫功能、介入致癌物的代谢、抑制癌细胞生长及抗过氧化作用等发挥防癌和抗癌功能。另外,硒对白血病的治疗引起了人们的重视。