共查询到19条相似文献,搜索用时 62 毫秒
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青蒿素及其衍生物的圆二色谱研究 总被引:4,自引:0,他引:4
本文通过对青蒿素及其16个衍生物的圆二色谱研究, 首交次确定了青蒿素衍衍生物8、9和17的过氧键的圆二色谱的λ~max和它的△s值。并对青蒿素衍生物的圆二色谱出现类似旋光谱中的“背景曲线”的异常现象作了探讨。 相似文献
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在体积分数为20%乙醇的Britton-Robinson缓冲溶液(pH=7.4)中,利用循环伏安法和紫外可见吸收光谱法研究了青蒿素与DNA的相互作用。电化学研究表明,DNA的存在能导致青蒿素在银电极上-0.672 V处的还原峰电流下降,峰电位正移。通过对比双链DNA(dsDNA)和单链(ssDNA)与青蒿素作用,得出青蒿素可嵌插到DNA分子中,形成非电活性的复合物。电化学方法可计算出DNA与青蒿素的结合比为1∶4,结合常数为3.6×104。电极过程的电化学参数表明,DNA作用前后,α、β值变化不明显,进一步证实了该复合物是非电活性;Ks值变小,表明二者作用后受扩散控制。紫外可见吸收光谱法研究表明,青蒿素对DNA分子发生嵌插作用。通过光谱滴定法可计算二者的结合比和结合常数,同样获得1个DNA结合4个青蒿素分子,结合常数为4.0×104,与电化学方法测定结果相吻合。实验数据显示,青蒿素进入细胞内有可能与细胞核中DNA结合,诱导细胞凋亡。 相似文献
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青蒿素1是中药青蒿(Artemisia annua L.)中的抗疟有效成份,它具有与其他抗疟药完全不同的独特结构,近年来,李英等已报道了从青蒿素合成得一系列疗效更高的衍生物,而Schmid等和许杏祥等曾分别独立完成了青蒿素的合成。由于合成其它青蒿素衍生物的需要,我们计划发展较为实用的方法。鉴于目前易于获得天然的青蒿素,因此我们在研究全合成的同时,也探索利用由青蒿素获得接力中间体重组青蒿素和合成青蒿素衍生物。通过酸性降解研究,我们从青蒿素经两步可制得双酮酯化合物3,产率较高。该化合物保持青蒿素中原有的构型,因此是一个理想的接力中间体,本文报道由此化合物重组青蒿素的工作。 相似文献
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本文首次报道从青蒿素(2)转变为△~(11(13))-脱氢青蒿素(1)的结果。青蒿素(2)在 LDA 存在下,与溴苯硒反应,得到11-苯硒基青蒿素(3)(27%)、11-溴代青蒿素(4)(15%),△~(11(13))-脱氢青蒿素(1)和△~(7(11)-脱氢青蒿素(5)(46%)。用二苯二硒的硒化反应只回收原料青蒿素。3用30%H_2O_2氧化,生成天然的1,产率95%。根据CD 光谱,推定3中的苯硒基和4中的溴原子均处于α-构型。 相似文献
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应用荧光光谱、紫外-可见光谱法研究了青蒿素与溶菌酶的相互作用,发现青蒿素对溶菌酶荧光有猝灭作用。以Lineweaver-Burk双倒数方程和能量传递原理分别计算了二者反应的结合常数(K25℃=646.4L/mol,K35℃=518.8L/mol)和作用距离(r=3.08nm)。实验表明,随着温度升高,溶菌酶与青蒿素的猝灭曲线斜率降低,证明了二者的相互结合作用为单一的静态猝灭过程,其作用机制属能量转移机制。通过测定热力学参数,判断了青蒿素和溶菌酶之间的作用力类型,青蒿素与溶菌酶以疏水作用力相结合,导致溶菌酶内源荧光的静态猝灭。通过青蒿素与溶菌酶的结合反应,探讨了药物青蒿素在生物体内与蛋白酶的相互作用机理。 相似文献
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Qinghaosu (QHS) and its derivatives are a new generation of antimalarial drugs characterized by fast action, high efficacy,
and good tolerance. This feature article states the discovery of QHS from traditional Chinese medicine qinghao (Artemisia annua L.) and reviews the progress during the past four decades in the research of phytochemistry of A. annua, chemical reactions and biotransformation of QHS, chemical synthesis and biosynthesis of QHS, synthesis and antimalarial
activity of QHS derivatives and analogs, pharmacological studies, clinical application, and the antimalarial mechanism. Undoubtedly,
QHS is an example of the value of traditional Chinese medicine in modern medicinal research. 相似文献
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《Bioelectrochemistry and bioenergetics (Lausanne, Switzerland)》1998,44(2):295-300
Artesunate is an important new antimalarial drug. The interaction of artesunate with hemin was investigated by electrochemical methods and UV spectroelectrochemistry (UV-SEC). Artesunate underwent an entirely irreversible reduction at ca. −1.27 V (vs. Ag/AgCl) on the glassy carbon electrode. Hemin can catalyze the decomposition of artesunate. In the presence of concentration of hemin as low as 2×10−8 M, the cathodic overpotential of artesunate was reduced ca. 680 mV (Epc=−0.59 V vs. Ag/AgCl). UV-SEC experiments further confirm this process. UV spectra show that the decomposed products of artesunate have absorption behavior similar to artesunate. These results indicated that artesunate might undergo the identical antimalarial mechanism as its parent compound Qinghaosu, and hemin plays a catalyst role in the process of action of Qinghaosu-type antimalarial drugs. 相似文献
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青蒿素抗疟机理研究最近的重要进展 总被引:2,自引:0,他引:2
1.论文名称UnifiedMechanisticFrameworkfortheFe(I)-InducedCleavageofQinghaosuandDerivatives/Analogues.TheFirstSpin-TrappingEvidence... 相似文献
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Artemisinin (also known as Qinghaosu), an active component of the Qinghao extract, is widely used as antimalarial drug. Previous studies reveal that artemisinin and its derivatives also have effective anti-inflammatory and immunomodulatory properties, but the direct molecular target remains unknown. Recently, several reports mentioned that myeloid differentiation factor 2 (MD-2, also known as lymphocyte antigen 96) may be the endogenous target of artemisinin in the inhibition of lipopolysaccharide signaling. However, the exact interaction between artemisinin and MD-2 is still not fully understood. Here, experimental and computational methods were employed to elucidate the relationship between the artemisinin and its inhibition mechanism. Experimental results showed that artemether exhibit higher anti-inflammatory activity performance than artemisinin and artesunate. Molecular docking results showed that artemisinin, artesunate, and artemether had similar binding poses, and all complexes remained stable throughout the whole molecular dynamics simulations, whereas the binding of artemisinin and its derivatives to MD-2 decreased the TLR4(Toll-Like Receptor 4)/MD-2 stability. Moreover, artemether exhibited lower binding energy as compared to artemisinin and artesunate, which is in good agreement with the experimental results. Leu61, Leu78, and Ile117 are indeed key residues that contribute to the binding free energy. Binding free energy analysis further confirmed that hydrophobic interactions were critical to maintain the binding mode of artemisinin and its derivatives with MD-2. 相似文献
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以INDO/S-CI法对青蒿素分子进行了量子化学研究。结合实验结果讨论了其紫外光谱和圆二色谱。 相似文献
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青蒿素1及其衍生物具有特征的过氧桥结构, 并呈现优秀的抗疟生物活性. 为了研究详细的作用机制和确定生物学作用靶标, 本研究从易得的青蒿素衍生物出发, 通过酰胺键相连, 合成了生物素标记的青蒿素衍生物. 相似文献
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Lanfranchi DA Belorgey D Müller T Vezin H Lanzer M Davioud-Charvet E 《Organic & biomolecular chemistry》2012,10(24):4795-4806
Menadione is the 2-methyl-1,4-naphthoquinone core used to design potent antimalarial redox-cyclers to affect the redox equilibrium of Plasmodium-infected red blood cells. Exploring the reactivity of fluoromethyl-1,4-naphthoquinones, in particular trifluoromenadione, under quasi-physiological conditions in NADPH-dependent glutathione reductase reactions, is discussed in terms of chemical synthesis, electrochemistry, enzyme kinetics, and antimalarial activities. Multitarget-directed drug discovery is an emerging approach to the design of new antimalarial drugs. Combining in one single 1,4-naphthoquinone molecule, the trifluoromenadione core with the alkyl chain at C-3 of the known antimalarial drug atovaquone, revealed a mechanism for CF(3) as a leaving group. The resulting trifluoromethyl derivative 5 showed a potent antimalarial activity per se against malarial parasites in culture. 相似文献
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The synthesis and antimalarial activity of six new 2-arylquinoline-4-methanols is described. The compounds bearing a sulfur were prepared to determine if antimalarial activity can be retained while photo-reactivity and phototoxicity is diminished by such substituents. The observed antimalarial activity of some of the new compounds show this to be possible. 相似文献
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Somruedee Jansongsaeng Nitipol Srimongkolpithak Jutharat Pengon Sumalee Kamchonwongpaisan Tanatorn Khotavivattana 《Molecules (Basel, Switzerland)》2021,26(13)
The rapid emergence of drug resistance to the current antimalarial agents has led to the urgent need for the discovery of new and effective compounds. In this work, a series of 5-phenoxy primaquine analogs with 8-aminoquinoline core (7a–7h) was synthesized and investigated for their antimalarial activity against Plasmodium falciparum. Most analogs showed improved blood antimalarial activity compared to the original primaquine. To further explore a drug hybrid strategy, a conjugate compound between tetraoxane and the representative 5-phenoxy-primaquine analog 7a was synthesized. In our work, the hybrid compound 12 exhibited almost a 30-fold increase in the blood antimalarial activity (IC50 = 0.38 ± 0.11 μM) compared to that of primaquine, with relatively low toxicity against mammalian cells (SI = 45.61). Furthermore, we found that these 5-phenoxy primaquine analogs and the hybrid exhibit significant heme polymerization inhibition, an activity similar to that of chloroquine, which could contribute to their improved antimalarial activity. The 5-phenoxy primaquine analogs and the tetraoxane hybrid could serve as promising candidates for the further development of antimalarial agents. 相似文献