Synthesis and evaluation of 2,9-disubstituted 8-phenylthio/phenylsulfinyl-9H-purine as new EGFR inhibitors

In present study, we described the synthesis and biological evaluation of a new class of EGFR inhibitors containing 2,9-disubstituted 8-phenylthio/phenylsulfinyl-9H-purine scaffold. Thirty-one compounds were synthesized. Among them, compound C9 displayed the IC₅₀ of 29.4?nM against HCC827 cell line and 1.9?nM against EGFR^L858R. Compound C12 showed moderate inhibitory activity against EGFR^{L858R/T790M/C797S} (IC₅₀?=?114?nM). Western bolt assay suggested that compound C9 significantly inhibited EGFR phosphorylation. In vivo test, compound C9 remarkably exhibited inhibitory effect on tumor growth at 5.0?mg/kg by oral administration in established nude mouse HCC827 xenograft model. These results indicate that the 2,9-disubstituted 8-phenylsulfinyl/phenylsulfinyl-9H-purine derivatives can act as potent EGFR(L858R) inhibitors and effective anticancer agents. Additionally, optimization of compound C12 may result in discovering the fourth-generation EGFR-TKIs.     

聚乙烯醇固定化酵母细胞制备CTP研究

以聚乙烯醇为固定化载体,固定化冷冻处理过的啤酒酵母细胞从CMP制备CTP;分别从胶的型号、浓度和固定化方法的优化等方面摸索了最适的固定化条件,固定化细胞在试验条件下连续发酵8次,转化率维持在85%～95%。同时,还对固定化细胞的稳定性进行试验研究,并用HPLC对产品进行了分离鉴定。     

一种新型眼皮肤白化病——OCA4

眼皮肤白化病(OCA)在遗传学上是一组由不同基因的突变导致的具有相同或相似临床症状的遗传病。根据涉及基因的不同, OCA进一步分为4型, 即眼皮肤白化病Ⅰ~Ⅳ型(OCA1~OCA4)。OCA4为近年新发现的一种眼皮肤白化病类型, 首报病例是一名土尔其后裔。与小鼠uw基因同源的MATP基因突变导致OCA4表型的发生。MATP 基因定位于5p13.3, 由7个外显子和6个内含子构成, MATP基因在转录水平上受黑素细胞特异性转录因子调控, 编码由530个氨基酸残基构成的膜相关转运蛋白。迄今, 至少已报道了18种MATP基因病理性突变和8种DNA多态性变异。     

中国人α珠蛋白基因-α3.7缺失亚型的研究

-α3.7是中国人常见的缺失型α-地中海贫血-2。根据重组位点的不同,-α3.7可分为-α3.7Ⅰ型、-α3.7Ⅱ型和-α3.7Ⅲ型,并且亚型的种类和频率具有种族差异性。本研究在中国人群中用PCR基因分析方法检出具有α珠蛋白基因-α3.7缺失的患者56例,然后用ApalⅠ和BalⅠ限制性内切酶进行分型。 结果表明,在这56例具有-α3.7缺失的患者中,有54例是-α3.7Ⅰ型,有2例是-α3.7Ⅱ型,尚未发现-α3.7Ⅲ型。此结果丰富了我国α地贫基因型谱的资料。 Abstract:-α3.7 is a common deletional α-thalassemia-2 in China.According to different recombination sites,-α3.7 can be divided into -α3.7Ⅰ、-α3.7Ⅱand -α3.7Ⅲ.The frequency and population distribution of these -α3.7 are quite different.In this study,we detected 56 patients among Chinese population of -α3.7 defect in alpha globin gene by PCR method,then the PCR product was digested by the restriction enzyme ApalⅠand BalⅠ.The sub-typing result shows that in the 56 cases of -α3.7 defect,54 out of 56 is -α3.7Ⅰ,2 out of 56 is -α3.7Ⅱ and none of -α3.7Ⅲ is detected.This result enriches the data about the alpha thalassemia genotypes of Chinese people.     

中国鲚属鱼类的矢耳石形态特征

分析了205尾分布于中国的4种2龄鲚属鱼类的矢耳石形态特征。结果显示,这4种鱼类的矢耳石都具有翼叶和基叶,但无后基叶和副基叶,中央突也不明显。背侧有脊突,叶形晶状突呈小三角形,仅限于腹侧。主凹槽明显,直管状,后端封闭。4种鱼矢耳石长轴长为体长的1.68%~2.82%,矢耳石重为体重的0.26‰~1.71‰;不论绝对重量或面积,均以七丝鲚和凤鲚的最大,刀鲚的次之,短颌鲚的最小,显现出与在海水中生活的时间呈正相关性。刀鲚和短颌鲚的矢耳石较轻薄,单位面积均重1.22~1.40mg/mm2;七丝鲚和凤鲚的较厚重,单位面积均重约1.86mg/mm2。矢耳石的长轴、短轴和单位重量等的变异系数,均要小于其体长特别是体重的变异系数,矢耳石形态的稳定性显著优于其身体形态的稳定性。     

北海抹香鲸的年龄鉴定

将2001年5月在广西琼州海峡获得的一头体长约18．0m的特大型雄性抹香鲸(Physeter macrocephalus)遗骸的下颌齿,用自制的器械将齿沿着纵向锯成厚约1～5mm的10个薄片,用600目和2000目的金砂纸精磨和抛光至约150μm。由9位具有用耳石或鳞片鉴定鱼类年龄经验的学者,用肉眼和解剖镜观察齿纵切面的微观结构和轮纹特征。根据对牙齿磨片牙骨质和牙齿齿质上的生长层组判断,其年龄约为29龄。     

中国大陆一新外来入侵种--刺桐姬小蜂

报道了最近发生在广东省深圳市、福建省厦门市等地刺桐等桐属植物上的一种新的外来人侵害虫——刺桐姬小蜂Quadrastichus erythrinae Kim。对其分类地位、形态特征、生物学特性、分布、寄主、为害症状等做了简要介绍,提出防治措施,并对其风险分析进行评估。     

Bacillus zhanjiangensis sp. nov., isolated from an oyster in South China Sea

A novel Gram-stain-positive, motile, catalase- and oxidase-positive, endospore-forming, aerobic, rod-shaped bacterium, designated strain JSM 099021^T, was isolated from an oyster collected from Naozhou Island in the South China Sea. Growth occurred with 0?C15% (w/v) NaCl (optimum 2?C4%) and at pH 6.0?C10.0 (optimum pH 7.5) and at 10?C45°C (optimum 30?C35°C). meso-Diaminopimelic acid was present in the cell-wall peptidoglycan. The predominant respiratory quinone was menaquinone 7 (MK-7) and the major polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. The major cellular fatty acids were anteiso-C15:0, anteiso-C17:0, iso-C15:0 and iso-C16:0. The genomic DNA G + C content was 39.5 mol%. A phylogenetic analysis based on 16S rRNA gene sequences indicated that strain JSM 099021^T belongs to the genus Bacillus, and was most closely related to the type strains of Bacillus halmapalus (sequence similarity 99.0%), Bacillus horikoshii (98.4%) and Bacillus cohnii (98.0%). The combination of phylogenetic analysis, DNA?CDNA hybridization, phenotypic characteristics and chemotaxonomic data supported the proposal that strain JSM 099021^T represents a new species of the genus Bacillus, for which the name Bacillus zhanjiangensis sp. nov. is proposed. The type strain was JSM 099021^T (=DSM 23010^T = KCTC 13713^T).