Design, Synthesis, and Biological Evaluation of Novel 1,2,4-Trioxanes as Potential Antimalarial Agents

被引：9
|
作者：
Gupta, Amit K. [1 ]
Varshney, Kanika [1 ]
Kumar, Vivek [2 ]
Srivastava, Kumkum [3 ]
Pant, Aditya B. [2 ]
Puri, Sunil K. [3 ]
Saxena, Anil K. [1 ]
机构：
[1] CSIR Cent Drug Res Inst, Med & Proc Chem Div, Lucknow 226031, Uttar Pradesh, India
[2] CSIR Indian Inst Toxicol Res, Vitro Toxicol Lab, Lucknow, Uttar Pradesh, India
[3] CSIR Cent Drug Res Inst, Div Parasitol, Lucknow, Uttar Pradesh, India
来源：
ARCHIV DER PHARMAZIE | 2017年 / 350卷 / 3-4期
关键词：
1,2,4-Trioxanes; Antimalarial; Drug design; Synthesis; QINGHAOSU ARTEMISININ; DRUG; NEUROTOXICITY;
D O I：
10.1002/ardp.201600335
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of substituted 1,2,4-trioxanes were synthesized and evaluated for their antimalarial potential, in silico ADME properties and cytotoxicity on neuronal cell lines. Among the 15 synthesized substituted 1,2,4-trioxanes, two compounds (compound 15, IC50=25.71nM; compound 21, IC50=19.6nM) exhibited promising in vitro antimalarial potential comparable to those of the existing drugs chloroquine and artemisinin. Both of these compounds were found to be nontoxic up to 20 mu M concentration in neuronal PC-12 cells. Compound 21 may serve as an optimized lead compound because of its less in vitro toxicity and lower probability to cross the blood brain barrier.
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页数：9
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