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Mingcheng Qian Xinyu Jiang Mingting Zhang Lijuan Hu Huimin Liu Shuai Zhao Xiaoying Zhou Xin Chen 《化学与生物多样性》2021,18(4):e2000979
In this article, we designed and synthesized two series of matrine analogs with ring-opening in the lactam portion of the molecule. Our in vitro cytotoxicity study showed that analog N-(3-bromophenyl)-4-[(1R,3aS,10aR,10bS)-decahydro-1H,4H-pyrido[3,2,1-ij][1,6]naphthyridin-1-yl]butanamide ( B11 ) with a meta-bromide on the phenyl ring displayed the best antiproliferative activity. Moreover, B11 induced cell cycle arrest in G1 phase and cell apoptosis in a dose-dependent manner in A549 cells. Molecular modeling revealed that B11 achieved a higher docking score compared to its precursor tert-butyl (1R,3aS,10aR,10bS)-1-[4-(3-bromoanilino)-4-oxobutyl]octahydro-1H,4H-pyrido[3,2,1-ij][1,6]naphthyridine-2(3H)-carboxylate ( A11 , an analog of B11 with a Boc group) and parent compound matrine, possibly because B11 formed a hydrogen bond with SER91 and a halogen bond with GLN320 on the binding site of annexin A2. Overall, we discovered the potential anticancer lead compound B11 , which can be used for further study both in vitro and in vivo. 相似文献
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The epimerization and dehydration reactions of the 17 beta-hydroxy group of anabolic 17 beta-hydroxy-17 alpha-methyl steroids have been investigated using the pyridinium salts of 17 beta-sulfate derivatives of methandienone 1, methyltestosterone 4, oxandrolone 7, mestanolone 10 and stanozolol 11 as model compounds. Rearrangement of the sulfate conjugates in buffered urine (pH 5.2) afforded the corresponding 17-epimers and 18-nor-17,17-dimethyl-13(14)-enes in a ratio of 0.8:1. These data indicated that both epimerization and dehydration of the 17 beta-sulfate derivatives were not dependent upon the respective chemical features of the steroids studied, but were instead inherent to the chemistry of the tertiary 17 beta-hydroxy group of these steroids. Interestingly, in vivo studies carried out with human male volunteers showed that only methandienone 1, methyltestosterone 4 and oxandrolone 7 yielded the corresponding 17-epimers 2, 5 and 8 and the 18-nor-17,17-dimethyl-13(14)-enes 3, 6 and 9 in ratios of 0.5:1, 2:1 and 2.7:1, respectively. No trace of the corresponding 17-epimers and 18-nor-17,17-dimethyl-13(14)-enes derivatives of mestanolone 10 and stanozolol 11 was detected in urine samples collected after administration of these steroids. These data suggested that the in vivo formation of the 17-epimers and 18-nor-17,17-dimethyl-13(14)-enes derivatives of 17 beta-hydroxy-17 alpha-methyl steroids is also dependent upon phase I and phase II metabolic reactions other than sulfation of the tertiary 17 beta-hydroxyl group, which are probably modulated by the respective chemical features of the steroidal substrates. The data reported in this study demonstrate that the 17-epimers and 18-nor-17,17-dimethyl-13(14)-enes are not artifacts resulting from the acidic or microbial degradation of the parent steroids in the gut as previously suggested by other authors, but arise from the rearrangement of their 17 beta-sulfate derivatives. Unchanged oxandrolone 7 was solely detected in the unconjugated steroid fraction whereas unchanged steroids 1, 4 and 11 were recovered from the glucuronide fraction. These data are indirect evidences suggesting that the glucuronide conjugates of compounds 1 and 4 are probably enol glucuronides and that of compound 11 is excreted in urine as a N-glucuronide involving its pyrazole moiety. The urinary excretion profiles of the epimeric and 18-nor-17,17-dimethyl-13(14)-ene steroids are presented and discussed on the basis of their structural features. 相似文献
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烟草愈伤组织分化和芽原基形成期间呼吸代谢途径的改变 总被引:3,自引:0,他引:3
接种在继代培养基上的柳叶烟草愈伤组织,未观察到组织分化和芽原基形成。在分化培养基上生长的愈伤组织,接种后第6天可见拟分生组织和管胞分化,9—12天有芽原基形成,15—18天可观察到苗端结构。根据碘乙酸、Na_3PO_4和丙二酸抑制试验,以及3-磷酸甘油醛脱氢酶与琥珀酸脱氢酶活性测定结果,初步表明烟草愈伤组织呼吸中存在有EMP、HMP和TCAC代谢途径.在发生输导组织和芽原基分化的愈伤组织中(接种后第6—12天),HMP途径的运行程度较高;而芽原基的继续生长(培养12天以后),则与EMP途径的增加有关;分化培养基上生长的愈伤组织,始终较继代培养愈伤组织具有较高的FCAC活性水平。 相似文献
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本文系用原子吸收光谱法测定了西安地区10例成人尸体和15例新生儿尸体的颅盖骨内Cu和zn的含量。结果求得成人颅骨中Cu正常含量(均数±标准差)为4.48±3.78mg/kg(干组织重);zn为597.05±472.54mg/kg。新生儿颅骨中Cu和zn的含量分别为1.96±0.76mg/kg;1160.38±859.71mg/kg。结果表明,成人颅骨内Cu含量高于新生儿,而成人颅骨内Zn含量显著低于新生儿。 相似文献
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SIRE-1 is a family of several hundred dispersed copies of a very large DNA element from Glycine max that has features characteristic of retroviruses and retrotransposons. A 2.4 kb SIRE-1-specific fragment was recovered from a soybean cDNA library and sequenced. The sequence contains two ORFs. Theoretical translation of ORF1 produces a gag-prot-like polyprotein containing highly conserved motifs found in retroelement nucleocapsids (CX2CX4HX4C) and aspartic proteases (LDSG). The second ORF is foreshortened. The cDNA also contains nearly 200 bp of a putative 5 LTR just upstream of a tRNA primer-binding site. 相似文献
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丙型肝炎病毒基因组部份NS5区蛋白基因在大肠杆菌中的表达 总被引:1,自引:0,他引:1
在大肠杆菌中表达了丙型肝炎病毒基因组NS5区A段和部份B段蛋白。NS5A蛋白溶于水,可经过GST亲和层析柱纯化;NS5B蛋白不溶于水,经PBS-Triton X-100洗涤,尿素溶解后,通过离子交换柱纯化。经SDS-PAGE和Westemblot分析,NS5A蛋白除在57kD左右有条带外,还有不同程度的降解产物;NS5B蛋白主要在58kD左右有条带出现。为查明表达蛋白抗体在病人血清中的分布,取9 相似文献
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非同位素PCR-单链构象多态性技术的建立和应用 总被引:2,自引:0,他引:2
PCR-单链构象多态性技术问世以来,成为研究基因突变的工具,特别是在分子肿瘤学研究中,广泛应用于癌基因,抑癌基因突变的研究,常规PCR-SSCP采用同位素标记PCR产物,测序板电泳分离突变,在操作和费用上有种种局限,文章建立了一种非同位素PCR-SSCP技术;通过不对称PCR获得单链,普通PAGE分离,经银染检出突变,用这种方法,还研究了四株鼻咽癌细胞株CNE1,CNE2,HK1和SUNE1中肿瘤 相似文献