Abstract：
:Histone acetylation is an extensively investigated post-translational modification that plays an important role as an epigenetic regulator. It is controlled by histone acetyl transferases (HATs) and histone deacetylases (HDACs). The overexpression of HDACs and consequent hypoacetylation of histones have been observed in a variety of different diseases, leading to a recent focus of HDACs as attractive drug targets. The natural product largazole is one of the most potent natural HDAC inhibitors discovered so far and a number of largazole analogs have been prepared to define structural requirements for its HDAC inhibitory activity. However, previous structure-activity relationship studies have heavily investigated the macrocycle region of largazole, while there have been only limited efforts to probe the effect of various zinc-binding groups (ZBGs) on HDAC inhibition. Herein, we prepared a series of largazole analogs with various ZBGs and evaluated their HDAC inhibition and cytotoxicity. While none of the analogs tested were as potent or selective as largazole, the Zn2+-binding affinity of each ZBG correlated with HDAC inhibition and cytotoxicity. We expect that our findings will aid in building a deeper understanding of the role of ZBGs in HDAC inhibition as well as provide an important basis for the future development of new largazole analogs with non-thiol ZBGs as novel therapeutics for cancer.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Kim B,Ratnayake R,Lee H,Shi G,Zeller SL,Li C,Luesch H,Hong Jdoi
10.1016/j.bmc.2017.03.071subject
Has Abstractpub_date
2017-06-15 00:00:00pages
3077-3086issue
12eissn
0968-0896issn
1464-3391pii
S0968-0896(17)30463-7journal_volume
25pub_type
杂志文章abstract：:We have surveyed the utility of Beckmann rearrangement for the conversion of indanones into carbostyrils. Initial attempts at the conversion of 6-methoxy indanone oxime under classical conditions resulted in the formation of the two unusual products: 2-sulfonyloxyindanone and the dimeric product. This unusual rearrang...
journal_title：Bioorganic & medicinal chemistry
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journal_title：Bioorganic & medicinal chemistry
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
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journal_title：Bioorganic & medicinal chemistry
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journal_title：Bioorganic & medicinal chemistry
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journal_title：Bioorganic & medicinal chemistry
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journal_title：Bioorganic & medicinal chemistry
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journal_title：Bioorganic & medicinal chemistry
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