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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Efficacy of Proton Pump Inhibitor Drugs against Plasmodium falciparum In Vitro and Their Probable Pharmacophores.
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Efficacy of Proton Pump Inhibitor Drugs against Plasmodium falciparum In Vitro and Their Probable Pharmacophores.

机译：质子泵抑制剂药物对恶性疟原虫的体外作用及其可能的药理作用。

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摘要

The substituted benzimidazoles omeprazole, lansoprazole, rabeprazole, and pantoprazole were found to have in vitro activity against three different isolates of Plasmodium falciparum: D6 (which is chloroquine and pyrimethamine sensitive), W2 (chloroquine and pyrimethamine resistant), and TM91C235 (multidrug resistant). Lansoprazole and rabeprazole were the most effective against all three isolates, with a 50% inhibitory concentration (IC(50)) range of 7 to 11 microM. Omeprazole showed intermediate activity against D6 and W2 isolates, with IC(50)s of 27 to 28 microM, but had poor activity against TM91C235, with an IC(50) of 76 microM. Pantoprazole was the least effective, with IC(50)s of 73 microM against D6, 53 microM against W2, and 39 microM against TM91C235. A pharmacophore model describing the important features responsible for potent activity of the drugs was developed using computational techniques of semiempirical quantum chemical methods and the three-dimensional QSAR procedure of the CATALYST software. The important features of the pharmacophore, according to the findings based on the CATALYST procedures, are the hydrogen bond acceptor and donor sites at the benzimidine nitrogen atoms and the two aromatic hydrophobic sites in the molecules. AM1 quantum chemical calculations identified the electrostatic potential surface surrounding the sulfoxide atom as crucial for potent activity.
机译：已发现取代的苯并咪唑奥美拉唑，兰索拉唑，雷贝拉唑和pan托拉唑对恶性疟原虫的三种不同分离株具有体外活性：D6（对氯喹和乙胺嘧啶敏感），W2（对氯喹和乙胺嘧啶敏感）和TM91C235（对多种药物耐药） 。兰索拉唑和雷贝拉唑对所有三种分离物最有效，抑制浓度（IC（50））的50％抑制范围为7至11 microM。奥美拉唑显示对D6和W2分离株具有中等活性，IC（50）为27至28 microM，但对TM91C235的活性较弱，IC（50）为76 microM。 top托拉唑效果最差，对D6的IC（50）为73 microM，对W2的IC（50）为39 microM，对TM91C235的IC（50）为39 microM。使用半经验量子化学方法的计算技术和CATALYST软件的三维QSAR程序，开发了一种药效团模型，描述了负责药物有效活性的重要特征。根据基于CATALYST方法的发现，药效基团的重要特征是在苯甲亚胺氮原子上的氢键受体和供体位点以及分子中的两个芳族疏水位点。 AM1量子化学计算确定了亚砜原子周围的静电势表面对于有效活性至关重要。

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