Department of Medicinal Chemistry and.
J Enzyme Inhib Med Chem. 2014 Aug;29(4):555-62. doi: 10.3109/14756366.2013.827675. Epub 2013 Sep 9.
HDAC inhibitors emerged as promising drug candidates in combating wide variety of cancers. At present, two of the compounds SAHA and Romidepsin were approved by FDA for cutaneous T-cell lymphoma and many are in various clinical phases. A new quinolone cap structure was explored with hydroxamic acid as zinc-binding group (ZBG). The pan HDAC inhibitory and antiproliferative activities against three human cancer cell lines HCT-116 (colon), NCI-H460 (lung) and U251 (glioblastoma) of the compounds (4a-4w) were evaluated. Introduction of heterocyclic amines in CAP region increased the enzyme inhibitory and antiproliferative activities and few of the compounds tested are metabolically stable in both MLM and HLM.
HDAC 抑制剂作为有前途的药物候选物，在对抗多种癌症方面具有显著疗效。目前，两种化合物 SAHA 和 Romidepsin 已被 FDA 批准用于治疗皮肤 T 细胞淋巴瘤，还有许多化合物处于不同的临床阶段。研究人员探索了一种新型喹诺酮 CAP 结构，其锌结合基团（ZBG）为羟肟酸。对化合物（4a-4w）进行了全 HDAC 抑制活性和对三种人癌细胞系 HCT-116（结肠）、NCI-H460（肺）和 U251（神经胶质瘤）的抗增殖活性评估。在 CAP 区域引入杂环胺可提高酶抑制和抗增殖活性，且一些测试化合物在 MLM 和 HLM 中均具有代谢稳定性。
