噻唑并杂环 hHDAC6 抑制剂的探索作为潜在的抗疟药物。
Exploration of thiaheterocyclic hHDAC6 inhibitors as potential antiplasmodial agents.
机构信息
SynBioC Research Group, Department of Sustainable Organic Chemistry & Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000, Ghent, Belgium.
Division of Pharmacology, Department of Medicine, University of Cape Town, K45, OMB Groote Schuur Hospital, Observatory 7925, South Africa.
出版信息
Future Med Chem. 2017 Mar;9(4):357-364. doi: 10.4155/fmc-2016-0215. Epub 2017 Mar 6.
AIM
The recurring resistance of the malaria parasite to many drugs compels the design of innovative chemical entities in antimalarial research. Pan-histone deacetylase inhibitors (pan-HDACis) have recently been presented in the literature as powerful novel antimalarials, although their application is hampered due to toxic side effects. This drawback might be neutralized by the deployment of isoform-selective HDACis.
RESULTS
In this study, 42 thiaheterocyclic benzohydroxamic acids, 17 of them being potent and selective hHDAC6 inhibitors, were tested to investigate a possible correlation between hHDAC6 inhibition and antiplasmodial activity.
CONCLUSION
Four hHDAC6 inhibitors showed submicromolar potency against both a chloroquine-sensitive and a chloroquine-resistant strain of Plasmodium falciparum with high selectivity indices, pointing to the relevance of exploring hHDAC6 inhibitors as potential new antiplasmodial agents.
目的
疟原虫对许多药物的反复耐药性迫使人们在抗疟研究中设计创新的化学实体。泛组蛋白去乙酰化酶抑制剂（pan-HDACis）最近在文献中被提出作为强大的新型抗疟药，尽管由于毒性副作用，它们的应用受到阻碍。这一缺点可以通过使用同工酶选择性 HDACis 来中和。
结果
在这项研究中，测试了 42 种噻杂环苯甲羟肟酸，其中 17 种是有效的、选择性的 hHDAC6 抑制剂，以研究 hHDAC6 抑制与抗疟活性之间可能存在的相关性。
结论
四种 hHDAC6 抑制剂对氯喹敏感和氯喹耐药的恶性疟原虫均表现出亚微摩尔的效力，且选择性指数高，这表明探索 hHDAC6 抑制剂作为潜在的新型抗疟药具有重要意义。
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