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.

引用

页数：9

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