Natural product-inspired aryl isonitriles as a new class of antimalarial compounds against drug-resistant parasites.
Natural product-inspired aryl isonitriles as a new class of antimalarial compounds against drug-resistant parasites.
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DOI：
10.1016/j.bmc.2020.115678
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发表时间：
2020-10-01
影响因子：
3.5
通讯作者：
Dai M
中科院分区：
文献类型：
--
作者：
Kyei-Baffour K;Davis DC;Boskovic Z;Kato N;Dai M
疟疾是一种流行的致命疾病。抗药性疟疾寄生虫的迅速出现使情况变得更糟。因此，开发新的化学实体，优选具有新的作用机制，是迫切和重要的。受复杂和稀缺的含异腈的萜烯天然产物的启发，我们评估了一系列易于制备的合成单和双异腈化合物，其中大部分具有简单但刚性的二苯乙烯骨架。从这个集合中，使用血液阶段增殖测定法鉴定了针对Dd2菌株的有效抗疟先导化合物。这些化合物包括31（EC50 = 88 nM）、41（EC50 = 68 nM）和43（EC50 = 27 nM）。初步SAR信息表明，异腈基对于所观察到的抗Dd2菌株的活性是必不可少的，并且双异腈化合物通常比相应的单异腈化合物表现更好。
Malaria is a prevalent and deadly disease. The fast emerging of drug resistant malaria parasites makes the situation even worse. Thus, developing new chemical entities, preferably with novel mechanisms of action, is urgent and important. Inspired by the complex and scarce isonitrile-containing terpene natural products, we evaluated a collection of easily prepared synthetic mono- and bis-isonitrile compounds, most of which feature a simple, but rigid stilbene backbone. From this collection, potent antimalarial lead compounds against the Dd2 strain using a blood stage proliferation assay were identified. These compounds include 31 (EC50 = 88 nM), 41 (EC50 = 68 nM), and 43 (EC50 = 27 nM). Preliminary SAR information showed that the isonitrile group is essential for the observed activity against the Dd2 strain and the bis-isonitrile compounds in general perform better than the corresponding mono-isonitrile compounds.
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影响因子：
7.3
作者：
Wright, AD;Wang, HQ;Tilley, L
通讯作者：
Tilley, L
影响因子：
64.8
作者：
Kato N;Comer E;Sakata-Kato T;Sharma A;Sharma M;Maetani M;Bastien J;Brancucci NM;Bittker JA;Corey V;Clarke D;Derbyshire ER;Dornan GL;Duffy S;Eckley S;Itoe MA;Koolen KM;Lewis TA;Lui PS;Lukens AK;Lund E;March S;Meibalan E;Meier BC;McPhail JA;Mitasev B;Moss EL;Sayes M;Van Gessel Y;Wawer MJ;Yoshinaga T;Zeeman AM;Avery VM;Bhatia SN;Burke JE;Catteruccia F;Clardy JC;Clemons PA;Dechering KJ;Duvall JR;Foley MA;Gusovsky F;Kocken CH;Marti M;Morningstar ML;Munoz B;Neafsey DE;Sharma A;Winzeler EA;Wirth DF;Scherer CA;Schreiber SL
通讯作者：
Schreiber SL
影响因子：
16.6
作者：
Tu, Youyou
通讯作者：
Tu, Youyou
影响因子：
56.9
作者：
KLAYMAN, DL
通讯作者：
KLAYMAN, DL
影响因子：
4.6
作者：
Mohammad, Haroon;Kyei-Baffour, Kwaku;Seleem, Mohamed N.
通讯作者：
Seleem, Mohamed N.