Synthesis and structure-activity relationships for new 6-fluoroquinoline derivatives with antiplasmodial activity

被引：13
|
作者：
Hochegger, Patrick [1 ]
Faist, Johanna [1 ]
Seebacher, Werner [1 ]
Saf, Robert [2 ]
Maser, Pascal [3 ,4 ]
Kaiser, Marcel [3 ,4 ]
Weis, Robert [1 ]
机构：
[1] Karl Franzens Univ Graz, Inst Pharmaceut Sci, Pharmaceut Chem, Schubertstr 1, A-8010 Graz, Austria
[2] Graz Univ Technol, ICTM, Stremayrgasse 9, A-8010 Graz, Austria
[3] Swiss Trop & Publ Hlth Inst, Socinstr 57, CH-4002 Basel, Switzerland
[4] Univ Basel, Peterspl 1, CH-4003 Basel, Switzerland
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2019年 / 27卷 / 10期
关键词：
Antimalarial; Plasmodium berghei; Plasmodium falciparum; Quinoline derivatives; PLASMODIUM-FALCIPARUM; RESISTANCE; DISCOVERY; RECEPTOR; INVITRO; POTENT; ASSAY;
D O I：
10.1016/j.bmc.2019.03.061
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The substitution of 6-fluoroquinolines was modified in ring positions 2 and 4. The new compounds were tested in vitro for their activities against a sensitive and a multidrug resistant strain of Plasmodium falciparum. Some physicochemical parametres were calculated (log P, log D, ligand efficiency) or determined experimentally (permeability). The most promising compounds were tested for their in vivo activity against Plasmodium berghei in a mouse model. The 6-fluoro-2-{4-[(4-methylpiperazin-1-yl)methyl]phenyl}-N-[2-(pyrrolidin-1-yl)ethyl]quinoline-4-carboxamide possessed proper physicochemical properties and showed high antiplasmodial activity in vitro (IC50 <= 0.0029 mu M) and in vivo (99.6% activity).
引用
收藏
页码：2052 / 2065
页数：14
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