Malaria Box-Inspired Discovery of N-Aminoalkyl-β-carboline-3-carboxamides, a Novel Orally Active Class of Antimalarials.
Malaria Box-Inspired Discovery of N-Aminoalkyl-β-carboline-3-carboxamides, a Novel Orally Active Class of Antimalarials.
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疟疾盒启发发现 N-氨基烷基-β-咔啉-3-甲酰胺，一种新型口服活性抗疟药。
DOI：
10.1021/acsmedchemlett.1c00663
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发表时间：
2022
影响因子：
4.2
通讯作者：
Carlier,PaulR
中科院分区：
文献类型：
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作者：
Mathew,Jopaul;Ding,Sha;Kunz,KevinA;Stacy,EmilyE;Butler,JoshuaH;Haney,ReaganS;Merino,EmilioF;Butschek,GrantJ;Rizopoulos,Zaira;Totrov,Maxim;Cassera,MariaB;Carlier,PaulR
使用源自抗疟药 MMV008138 的药效团对公开的抗疟药命中数据库进行虚拟配体筛选，发现 TCMDC-140230（一种四氢-β-咔啉酰胺）值得探索。合成了该结构的所有四种立体异构体，但没有一种能够有效抑制疟原虫恶性疟原虫的生长。有趣的是，7e（这些合成的一种次要副产品）被证明在体外具有抗 P 的功效。 falciparumand 在疟疾体内小鼠模型中口服有效（40 mg/kg）。
Virtual ligand screening of a publicly available database of antimalarial hits using a pharmacophore derived from antimalarial MMV008138 identified TCMDC-140230, a tetrahydro-β-carboline amide, as worthy of exploration. All four stereoisomers of this structure were synthesized, but none potently inhibited growth of the malaria parasitePlasmodium falciparum. Interestingly,7e, a minor byproduct of these syntheses, proved to be potentin vitroagainstP. falciparumand was orally efficacious (40 mg/kg) in anin vivomouse model of malaria.