Chimeric HDAC inhibitors: Comprehensive review on the HDAC-based strategies developed to combat cancer

被引:126
作者
Hesham, Heba M. [1 ]
Lasheen, Deena S. [1 ]
Abouzid, Khaled A. M. [1 ]
机构
[1] Ain Shams Univ, Fac Pharm, Dept Pharmaceut Chem, Cairo 11566, Egypt
关键词
cancer resistance; cancer stem cell; chimeric anticancer agents; dual action HDAC inhibitors; molecular hybridization; HISTONE DEACETYLASE INHIBITORS; INOSINE MONOPHOSPHATE DEHYDROGENASE; TARGETING PROSTATE-CANCER; ENDOTHELIAL GROWTH-FACTOR; PROTEIN-KINASE CK2; DUAL INHIBITORS; HYDROXAMIC ACID; DRUG-RESISTANCE; BIOLOGICAL EVALUATION; MOLECULAR DOCKING;
D O I
10.1002/med.21505
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Recently, molecular hybridization paradigm became an interesting and smart way to defeat the multifaceted cancer disease by a single molecular entity that acts via several mechanisms just like a magic bullet. Also, HDAC is an important epigenetic target in drug discovery, and the HDAC inhibitors showed successful pattern as cytotoxic agents. Because of their flexible structure activity relationship, it was easy to link them to other anticancer scaffolds. So, many dual action HDAC inhibitors have been developed and most of these hybrids have higher potency than the constituting parents in fighting of the cancer cells. This review describes potential applications of chimeric HDAC inhibitors, which simultaneously modulate not only HDAC but also multiple targets, in treatment of relapsing and drug-resistant cancers. We have nearly collected most of the reported dual action HDAC inhibitors yet to provide a comprehensive guide for the drug discovery process for developing more efficient anticancer agents.
引用
收藏
页码:2058 / 2109
页数:52
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