A series of bisthiazole-based hydroxamic acids as novel potent HDAC inhibitors was developed during our previous work. In the present work, a new series of highly potent bisthiazole-based compounds were designed and synthesized. Among the prepared compounds, compound H13, which contains an α-(S)-methyl-substituted benzyl group, displays potent inhibitory activity toward human HDACs and several cancer cells lines. Compound H13 has a favorable PK profile and high tissue distribution specificity in the colon, as well as good efficacy in the AOM-DSS mouse model for colitis-associated colonic tumorigenesis.

中文翻译：

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组织特异性联苯并噻唑组蛋白去乙酰化酶（HDAC）抑制剂的合成，体外和体内生物学评估。

在我们以前的工作中，开发了一系列基于联噻唑的异羟肟酸作为新型强效HDAC抑制剂。在目前的工作中，设计并合成了一系列新的高效基于联噻唑的化合物。在制备的化合物中，含有α-（S）-甲基取代的苄基的化合物H13显示出对人HDAC和几种癌细胞系的有效抑制活性。化合物H13在结肠中具有良好的PK分布和高组织分布特异性，并且在AOM-DSS小鼠模型中具有与结肠炎相关的结肠肿瘤发生的良好功效。