Orthosteric-allosteric dual inhibitors of PfHT1 as selective antimalarial agents was written by Huang, Jian;Yuan, Yafei;Zhao, Na;Pu, Debing;Tang, Qingxuan;Zhang, Shuo;Luo, Shuchen;Yang, Xikang;Wang, Nan;Xiao, Yu;Zhang, Tuan;Liu, Zhuoyi;Sakata-Kato, Tomoyo;Jiang, Xin;Kato, Nobutaka;Yan, Nieng;Yin, Hang. And the article was included in Proceedings of the National Academy of Sciences of the United States of America in 2021.Recommanded Product: (3aR,5S,6S,6aR)-5-((R)-2,2-Dimethyl-1,3-dioxolan-4-yl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol This article mentions the following:
Artemisinin-resistant malaria parasites have emerged and have been spreading, posing a significant public health challenge. Antimalarial drugs with novel mechanisms of action are therefore urgently needed. In this report, we exploit a ‘selective starvation’ strategy by inhibiting Plasmodium falciparum hexose transporter 1 (PfHT1), the sole hexose transporter in P. falciparum, over human glucose transporter 1 (hGLUT1), providing an alternative approach to fight against multidrug-resistant malaria parasites. The crystal structure of hGLUT3, which shares 80% sequence similarity with hGLUT1, was resolved in complex with C3361, a moderate PfHT1-specific inhibitor, at 2.3-Å resolution Structural comparison between the present hGLUT3-C3361 and our previously reported PfHT1-C3361 confirmed the unique inhibitor binding-induced pocket in PfHT1. We then designed small mols. to simultaneously block the orthosteric and allosteric pockets of PfHT1. Through extensive structure-activity relationship studies, the TH-PF series was identified to selectively inhibit PfHT1 over hGLUT1 and potent against multiple strains of the blood-stage P. falciparum. Our findings shed light on the next-generation chemotherapeutics with a paradigm-shifting structure-based design strategy to simultaneously target the orthosteric and allosteric sites of a transporter. In the experiment, the researchers used many compounds, for example, (3aR,5S,6S,6aR)-5-((R)-2,2-Dimethyl-1,3-dioxolan-4-yl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol (cas: 582-52-5Recommanded Product: (3aR,5S,6S,6aR)-5-((R)-2,2-Dimethyl-1,3-dioxolan-4-yl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol).
(3aR,5S,6S,6aR)-5-((R)-2,2-Dimethyl-1,3-dioxolan-4-yl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol (cas: 582-52-5) belongs to tetrahydrofuran derivatives. Tetrahydrofuran and dihydrofuran form the basic structural unit of many naturally occurring scaffolds like gambieric acid A and ciguatoxin, goniocin, and some biologically active molecules. Tetrahydrofuran reaction with hydrogen sulfide: In the presence of a solid acid catalyst, tetrahydrofuran reacts with hydrogen sulfide to give tetrahydrothiophene.Recommanded Product: (3aR,5S,6S,6aR)-5-((R)-2,2-Dimethyl-1,3-dioxolan-4-yl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol
Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem