Simplified Reversed Chloroquines To Overcome Malaria Resistance to Quinoline-Based Drugs

被引:12
作者
Gunsaru, Bornface [1 ]
Burgess, Steven J. [1 ,2 ]
Morrill, Westin [2 ]
Kelly, Jane X. [1 ,2 ,3 ]
Shomloo, Shawheen [1 ,2 ]
Smilkstein, Martin J. [3 ]
Liebman, Katherine [1 ]
Peyton, David H. [1 ,2 ]
机构
[1] Portland State Univ, Dept Chem, Portland, OR 97207 USA
[2] DesignMedix Inc, Portland, OR 97210 USA
[3] Portland VA Med Ctr, Portland, OR USA
基金
美国国家卫生研究院;
关键词
chloroquine; Plasmodium falciparum; antimalarial; drug discovery; accumulation; hemozoin; hematin; structure-activity relationship; drug development; malaria; drug resistance; PLASMODIUM-FALCIPARUM CHLOROQUINE; BETA-HEMATIN FORMATION; ANTIMALARIAL-DRUGS; RODENT MALARIA; IN-VITRO; TRANSPORTER; PRIMAQUINE; MECHANISM; DISCOVERY; TRAVELERS;
D O I
10.1128/AAC.01913-16
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Building on our earlier work of attaching a chemosensitizer (reversal agent) to a known drug pharmacophore, we have now expanded the structure-activity relationship study to include simplified versions of the chemosensitizer. The change from two aromatic rings in this head group to a single ring does not appear to detrimentally affect the antimalarial activity of the compounds. Data from in vitro heme binding and beta-hematin inhibition assays suggest that the single aromatic RCQ compounds retain activities against Plasmodium falciparum similar to those of CQ, although other mechanisms of action may be relevant to their activities.
引用
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页数:13
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