Wang, Manjiong; Tang, Tongke; Li, Ruoxi; Huang, Zhenghui; Ling, Dazheng; Zheng, Lulu; Ding, Yan; Liu, Taiping; Xu, Wenyue; Zhu, Feng; Min, Hui; Boonhok, Rachasak; Mao, Fei; Zhu, Jin; Li, Xiaokang; Jiang, Lubin; Li, Jian published the artcile< Drug Repurposing of Quisinostat to Discover Novel Plasmodium falciparum HDAC1 Inhibitors with Enhanced Triple-Stage Antimalarial Activity and Improved Safety>, HPLC of Formula: 89793-12-4, the main research area is quisinostat derivative preparation resistant malaria drug repurposing.
Our previous work found that the clin. histone deacetylase (HDAC) inhibitor quisinostat exhibited a significant antimalarial effect but with severe toxicity. In this work, 35 novel derivatives were designed and synthesized based on quisinostat as the lead compound, and their in vitro antimalarial activities and cytotoxicities were systematically evaluated. Among them, JX35 showed potent inhibition against both wild-type and multidrug-resistant parasite strains and displayed a significant in vivo killing effect against all life cycles of parasites, including the blood stage, liver stage, and gametocyte stage, indicating its potential for the simultaneous treatment, chemoprevention, and blockage of malaria transmission. Compared with quisinostat, JX35 exhibited stronger antimalarial efficacy, more adequate safety, and good pharmacokinetic properties. Addnl., mechanistic studies via mol. docking studies, induced PfHDAC1/2 knockdown assays, and PfHDAC1 enzyme inhibition assays jointly indicated that the antimalarial target of JX35 was PfHDAC1. In summary, we discovered the promising candidate PfHDAC1 inhibitor JX35, which showed stronger triple-stage antimalarial effects and lower toxicity than quisinostat.
Journal of Medicinal Chemistry published new progress about Antimalarials. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, HPLC of Formula: 89793-12-4.
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia