School of Biological Science & Technology, University of Jinan, Jinan, Shandong, 250022, China.
Shanghai Key Laboratory of Regulatory Biology, The Institute of Biomedical Sciences & School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Future Med Chem. 2020 Apr;12(8):655-672. doi: 10.4155/fmc-2019-0343. Epub 2020 Mar 23.
Histone deacetylases (HDACs) are one of the validated targets for cancer treatments. In our previous work, we designed a series of bis-substituted aromatic amide HDAC inhibitors (HDACis), among which compounds and showed promising anticancer effects. However, the low solubilities prevented their subsequent developments. We developed additional thiophene-based hydroxamate HDACis in order to improve their physicochemical properties. biological evaluations of these analogs revealed potent antiproliferative and antimigrated activities. More importantly, compound exhibited excellent antitumor activities in MDA-MB-231 xenograft model mice. Furthermore, showed better anticancer activities and drug-like properties than . Our results proved that thiophene-based hydroxamate HDACis can serve as a promising framework for developing potential anticancer agents.
组蛋白去乙酰化酶（HDACs）是癌症治疗的一个已验证的靶点。在我们之前的工作中，我们设计了一系列双取代芳香酰胺 HDAC 抑制剂（HDACis），其中化合物 和 显示出有希望的抗癌效果。然而，低溶解度阻碍了它们的进一步发展。我们开发了额外的噻吩基羟肟酸 HDACis，以改善它们的物理化学性质。这些类似物的生物学评估显示出强大的抗增殖和抗迁移活性。更重要的是，化合物 在 MDA-MB-231 异种移植模型小鼠中表现出优异的抗肿瘤活性。此外， 比 表现出更好的抗癌活性和类药性。我们的结果证明，噻吩基羟肟酸 HDACis 可以作为开发潜在抗癌药物的有前途的框架。
