4-S-(5″-烃基-4″-氨基-1″,2″,4″-三唑-3″-基)-4-去氧-4′-去甲基表鬼臼毒素衍生物的合成及抗肿瘤活性

许多有显著抗肿瘤活性的鬼臼毒素类化合物,其母核C-4侧链上往往连接有刚性较强的脂环或芳香环结构,而且侧链多含有一定数量的杂原子［1～3］。另外,三氮唑类化合物大都有广泛的生物活性,如抗菌［4～5］、抗病毒［6］、抗肿瘤［7］等,据此,我们设计并合成了8个三氮唑杂环取代的表鬼臼毒素衍生物,以期寻找活性高、毒副作用小的鬼臼毒素类药物,并进一步考察此类化合物的构效关系。　合成路线如图1所示,三氮唑3a～3h和4′-去甲基-表鬼臼毒2分别按文献［8,9］方法合成;我们选择三氟乙酸作为缩合剂,基于它不仅能催化缩合反应,而且能保护三唑上的氨基官能团,使其不能充当进攻基团;最后一步缩合反应显然经历了一个SN1历程,4′-去甲基-表鬼臼毒 的C-4位上很容易形成一个苄基型碳正离子,由于C-1位有庞大的芳环,加之,进攻的基团也较大,可以预料,这个反应有很强的立体选择性,使C-4β-构型成为主要产物,事实确实如此,在TLC上几乎看不到C-4α-构型的产物。     

Transforming tonic firing into a rhythmic output in the Aplysia feeding system: presynaptic inhibition of a command-like neuron by a CpG element

Tonic stimuli can elicit rhythmic responses. The neural circuit underlying Aplysia californica consummatory feeding was used to examine how a maintained stimulus elicits repetitive, rhythmic movements. The command-like cerebral-buccal interneuron 2 (CBI-2) is excited by tonic food stimuli but initiates rhythmic consummatory responses by exciting only protraction-phase neurons, which then excite retraction-phase neurons after a delay. CBI-2 is inhibited during retraction, generally preventing it from exciting protraction-phase neurons during retraction. We have found that depolarizing CBI-2 during retraction overcomes the inhibition and causes CBI-2 to fire, potentially leading CBI-2 to excite protraction-phase neurons during retraction. However, CBI-2 synaptic outputs to protraction-phase neurons were blocked during retraction, thereby preventing excitation during retraction. The block was caused by presynaptic inhibition of CBI-2 by a key buccal ganglion retraction-phase interneuron, B64, which also causes postsynaptic inhibition of protraction-phase neurons. Pre- and postsynaptic inhibition could be separated. First, only presynaptic inhibition affected facilitation of excitatory postsynaptic potentials (EPSPs) from CBI-2 to its followers. Second, a newly identified neuron, B54, produced postsynaptic inhibition similar to that of B64 but did not cause presynaptic inhibition. Third, in some target neurons B64 produced only presynaptic but not postsynaptic inhibition. Blocking CBI-2 transmitter release in the buccal ganglia during retraction functions to prevent CBI-2 from driving protraction-phase neurons during retraction and regulates the facilitation of the CBI-2 induced EPSPs in protraction-phase neurons.     

EphB2受体及其配体Ephrin-B在结直肠癌中的研究进展

EphB2受体及其配体Ephrin-B系统的功能失调将导致肠上皮具有增殖能力细胞沿着隐窝-鞭毛轴杂乱排列;而且在结直肠癌患者癌组织中,EphB2的表达越低,浸润深度越深,分化越差,远处转移越多,存活率越低;体外实验也证明其高表达在癌细胞菌落形成实验可抑制癌细胞的生长,配体Ephrin-B对EphB2受体的激活可降低肿瘤细胞的侵袭性.在本文中我们将就EphB2/Ephrin-B系统关于肠上皮干细胞迁徙导向的调控,及其在大肠癌的多步癌变过程中的抑制作用的最新研究进展加以综述.     

一个新型的双二萜生物碱

普格乌头(Aconitum pukeense W.T.Wang)分布于云南东北部和四川西南部,生长在海拔3400～3500米山地谷中竹林边或沟边。因其根部毒性很强,可用作箭毒,在云南巧家药山又称之为弩箭药。民间常将其泡制后用于治疗跌打损伤等症。该植物的化学成     

人尿中沙丁胺醇的测定

采用GC—Ms联用技术，对尿中的沙丁胺醇(salbutamol)进行分析。实验表明，口服一片沙丁胺醇(2．4 mg)，可于24 h从尿中排泄，且以游离形式为主。样品提取时，控制溶液pH为8.8时，提取率较高。本方法对沙丁胺醇定性简单、快速、准确。     

中药大黄质量的化学模式识别

本文用PRIMA法对大黄属(Rheum)6种植物的29个样品的质量进行了化学模式识别研究。以泻下药理实验的结果佐证、核对。根据35维HPLC数据或16维UV数据,与SIMCA法、Bayes判别法、非线性映照法(NLM)等模式识别法比较,PRIMA法具有计算速度快、适用范围广的特点,比植物形态学方法的正确率高。本文还根据一阶导数紫外光谱提供的数据,简化了化学模式识別法鉴定中药大黄的操作步骤。     

Circadian modulation of complex learning in diurnal and nocturnal Aplysia

Understanding modulation of memory, as well as the mechanisms underlying memory formation, has become a key issue in neuroscience research. Previously, we found that the formation of long-term, but not short-term, memory for a nonassociative form of learning, sensitization, was modulated by the circadian clock in the diurnal Aplysia californica. To define the scope of circadian modulation of memory, we examined an associative operant learning paradigm, learning that food is inedible (LFI). Significantly greater long-term memory of LFI occurred when A. californica were trained and tested during the subjective day, compared with animals trained and tested in the subjective night. In contrast, animals displayed similar levels of short-term memory for LFI when trained in either the subjective day or night. Circadian modulation of long-term memory for LFI was dependent on the time of training, rather than the time of testing. To broaden our investigation of circadian modulation of memory, we extended our studies to a nocturnal species, Aplysia fasciata. Contrary to the significant memory observed during the day with the diurnal A. californica, A. fasciata showed no long-term memory for LFI when trained during the day. However, A. fasciata demonstrated significant long-term memory when trained and tested during the night. Thus, the circadian clock modulates memory formation in phase with the animals' activity period. The results from our studies of circadian modulation of long-term sensitization and LFI suggest that circadian modulation of memory formation may be a general phenomenon with potentially widespread implications for many types of long-term learning.