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801.
802.
Peter J. Choi Hamish S. Sutherland Amy S.T. Tong Adrian Blaser Scott G. Franzblau Christopher B. Cooper Manisha U. Lotlikar Anna M. Upton Jerome Guillemont Magali Motte Laurence Queguiner Koen Andries Walter Van den Broeck William A. Denny Brian D. Palmer 《Bioorganic & medicinal chemistry letters》2017,27(23):5190-5196
Analogues of bedaquiline where the phenyl B-unit was replaced with monocyclic heterocycles of widely differing lipophilicity (thiophenes, furans, pyridines) were synthesised and evaluated. While there was an expected broad positive correlation between lipophilicity and anti-TB activity, the 4-pyridyl derivatives appeared to have an additional contribution to antibacterial potency. The majority of the compounds were (desirably) more polar and had higher rates of clearance than bedaquiline, and showed acceptable oral bioavailability, but there was only limited (and unpredictable) improvement in their hERG liability. 相似文献
803.
探索用重组8型腺相关病毒载体携带1.3拷贝乙型肝炎病毒(rAAV8-1.3HBV)介导的HBV持续感染小鼠模型评价核苷酸类似物抗病毒药物的抗病毒效果.首先,通过将rAAV8-1.3HBV经尾静脉注射到30只C57BL/6小鼠体内,建立HBV持续感染模型并对模型成功率进行检测,将建模成功的27只小鼠随机分成6组.然后采取灌胃的方式给予不同剂量的抗病毒药物恩替卡韦(ETV)及拉米夫定(LAM),每日1次,连续l0d,后停药15d,同时设置生理盐水及空白对照组.其中ETV分为高剂量(1.0 mg/(kg·d))和低剂量(0.1 mg/(kg·d) 两组;LAM分为高剂量(500 mg/(kg·d)) 和低剂量(100 mg/(kg·d)) 两组.检测给药前后和停药前后小鼠模型血清中HBV DNA、HBeAg和HBsAg表达水平并比较变化情况.结果发现连续给药10d后,各给药组与生理盐水组相比,血清中HBV DNA水平均显著下降,具有统计学差异(P<0.05).停药15d后,低剂量的ETV与LAM两组血清HBV DNA水平出现反弹,差异存在统计学意义(P<0.05).在整个实验过程中,各组小鼠血清中HBeAg和HBsAg表达水平均未出现明显变化.上述结果表明,ETV和LAM能有效抑制模型小鼠中HBV病毒的复制,而对HBeAg和HBsAg表达水平无明显影响;提示AAV8-1.3HBV介导的HBV持续感染小鼠模型制备简单,成模率高,可有效体现出ETV和LAM抗HBV的作用效果,从而用于核苷酸类似物抗HBV药物的筛查. 相似文献
804.
Ma?der?Pagadoy Fran?oise?Peypoux Jean?WallachEmail author 《International journal of peptide research and therapeutics》2005,11(3):195-202
Using the Fmoc methodology, we report the chemical synthesis of surfactin and of four of its analogues, by stepwise solid-phase peptide synthesis (SPPS) on Sasrin resin. Formation of depsipeptide bond was performed with EDC (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide. In developing our strategy, surfactin was used as a model and we synthesized both its racemic mixture and its R isoform. (R) 3-hydroxy fatty acid was obtained using Candida antarctica lipase from the racemic fatty acid, allowing a further identification of both R and S isoforms in the racemic mixture. Analogues were synthesized as racemic linear lipopeptides. Then, both enantiomers were separated and purified by adsorption chromatography on silicic acid, following cleavage from the resin. Linear R lipoheptapeptides were identified by TLC. They exhibit, in all cases, higher Rf values than those of the corresponding S isoforms. Cyclization was then performed independently for each enantiomer, using a HATU/DIEA coupling in solution. The yields were highly dependent on the position and on the nature of the modified amino acids. 相似文献
805.
本文报道了茼蒿素类似物对小菜蛾的产卵忌避作用,对卵孵化的延缓作用、杀卵作用及对幼虫的毒杀作用。结果表明:茼蒿素类似物对小菜蛾具有一定的产卵忌避作用,在1000μg/ml的浓度下,4号、8与、12号和20号化合物的产卵忌避作用分别为39.90%、57.90%、25.56%和47.14%;4种化合物均能延缓卵的卵化并具有一定的杀卵作用;8号、12号和20号化合物对小菜蛾2龄幼虫的LC50分别为582. 相似文献
806.
807.
表油菜素内酯对黄瓜幼苗下胚轴过氧化物酶和IAA氧化酶活性的影响 总被引:1,自引:0,他引:1
黄瓜幼苗用0.1~1 ppm表油菜素内酯(epiBR)处理1~3d后,下胚轴中过氧化物酶活性明显低于对照;随着处理浓度的增加和处理时间的延长,与对照之间的差别愈趋增大。当浓度高于1ppm时,过氧化物酶的活性不再继续降低。表油菜素内醋对过氧化物酶活性的这种抑制作用需经约1O h的滞后期。IAA氧化酶的活性变化与过氧化物酶相似,epiBR处理时间愈长酶活性增加愈趋缓慢。 经IAA处理的下胚轴,过氧化物酶和IAA氧化酶的活性变化与对照无明显差异。这提示油菜素内酯与IAA促进生长可能是通过不同的作用方式。 相似文献
808.
【背景】近年来骨化醇类化合物(活性维生素D及其类似物)在肿瘤治疗、免疫调节中的作用逐渐被发现,药用价值显著,但目前化学合成法制备困难,因此高效制备骨化醇类化合物成为研究热点。【目的】利用假诺卡氏菌(Pseudonocardiasp.)转化骨化醇类底物分子并提高转化率。【方法】从化学合成方法常用的原料及中间体中筛选能被有效转化的底物分子,利用单因素及正交试验对转化条件进行优化。【结果】筛选到阿法骨化醇(Alfacalcidol,1α-(OH)VD3)、艾地骨化醇中间体(Eldecalcitolintermediate, AD-M07)、帕立骨化醇中间体(Paricalcitol intermediate,PC-M07) 3种底物分子,分别被转化为骨化三醇(Calcitriol,1α,25(OH)2VD3)、艾地骨化醇中间体(Eldecalcitol intermediate,AD-M08)、帕立骨化醇(Paricalcitol,PC)。确定最优转化条件:蛋白胨20.0 g/L,葡萄糖15.0 g/L,部分甲基化的β-环糊精(PMCD) 0.5%(质量体积比),转化温度25-30°C,接种量5%-10%(体积比),转化时间72、72、96 h,底物浓度1.2、0.6、0.6mg/mL,初始pH6.0-8.0。在此条件下3种底物的最高转化率分别达到85%、96%、75%。【结论】通过转化条件的优化3种产物的转化率大幅提高,为更加快速高效地利用微生物转化法制备骨化醇类化合物提供参考。 相似文献
809.
Effects of plant growth regulators on the antioxidant system in callus of two maize cultivars subjected to water stress 总被引:10,自引:0,他引:10
The effects of brassinolide, uniconazole and methyl jasmonate on several aspects of antioxidant defences, were studied in callus tissues of drought-resistant (PAN 6043) and drought-sensitive (SC 701) cultivars of maize. When regulator-treated calli were subjected to water stress with PEG for 24 h the activities of antioxidant enzymes, such as superoxide dismutase, catalase, ascorbate peroxidase, peroxidase and glutathione reductase, remained higher in callus of the drought-resistant than in callus of the drought-sensitive cultivar. Damage, as indicated by the levels of hydrogen peroxide and malondialdehyde, the reduction of ascorbate and carotenoids, and leakage of electrolytes from cells was apparent in callus of both cultivars as a consequence of the applied water stress. However, the damage was less marked in the drought-resistant cultivar. The regulator-treated callus of this cultivar also had a higher survival percentage than that of the drought-sensitive cultivar.The present results also compare the effects of growth regulators on antioxidant systems in callus tissue of different drought-resistant cultivars when exposed to paraquat and water stress. 相似文献
810.
Janet P. Slovin 《Plant Growth Regulation》1997,21(3):215-221
Two strategies for selection of plant mutants altered in their ability to hydrolyze IAA conjugates are described. The rationale for both strategies is to form a conjugate between two chemical moieties in which one moiety is a toxin. The first strategy makes use of a toxic auxin analogue. For this approach a series of halogenated IAA analogues were tested for toxic properties to Lemna gibba and Zea mays. Several halogenated analogues were toxic, but only 5-Br-IAA was highly toxic to both species. The second strategy required a toxic compound with suitable functional groups to allow IAA conjugation. The mycotoxin patulin was found to be a suitable candidate. Uptake and hydrolysis of IAA-conjugates was studied in order to better define the conditions required for conjugate analogues to be effectively employed for selections. 相似文献