Design and synthesis of mono and bicyclic tetrapeptides thioester as potent inhibitor of histone deacetylases

被引：8

作者：

Hoque, Md. Ashraful ^{[1
,2
,3
]}

Islam, Md. Shahidul ^{[3
,4
]}

Islam, Md. Nurul ^{[3
,4
]}

Kato, Tamaki ^{[3
]}

Nishino, Norikazu ^{[3
]}

Ito, Akihiro ^{[5
]}

Yoshida, Minoru ^{[5
]}

机构：

[1] Univ Putra Malaysia, Dept Chem, Fac Sci, Serdang 43400, Malaysia

[2] Rajshahi Univ, Dept Biochem & Mol Biol, Fac Sci, Rajshahi 6205, Bangladesh

[3] Kyushu Inst Technol, Grad Sch Life Sci & Syst Engn, Kitakyushu, Fukuoka 8080196, Japan

[4] Rajshahi Univ, Dept Chem, Fac Sci, Rajshahi 6205, Bangladesh

[5] RIKEN, Wako, Saitama 3510198, Japan

来源：

AMINO ACIDS | 2014年 / 46卷 / 10期

关键词：

Histone deacetylase inhibitors; Depsipeptide; Largazole; Bicyclic tetrapeptides; ACETYLATION; BEARING; ANALOGS; ACID;

D O I：

10.1007/s00726-014-1800-5

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Inhibitors of histone deacetylases (HDACs) are a promising class of anticancer agents that have an effect on gene regulation. The naturally occurring cyclic depsipeptide FK228 containing disulfide and Largazole possessing thioester functionalities act as pro-drugs and share the same HDAC inhibition mechanism in cell. Inspired from these facts, we have reported bicyclic tetrapeptide disulfide HDAC inhibitors resembling FK228 with potent activity and enhanced selectivity. In the present study, we report the design and synthesis of several mono and bicyclic tetrapeptide thioester HDAC inhibitors that share the inhibition mechanism similar to Largazole. Most of the compounds showed HDAC1 and HDAC4 inhibition and p21 promoting activity in nanomolar ranges. Among these the monocyclic peptides 1, 2 and bicyclic peptide, 4 are notable demanding more advanced research to be promising anticancer drug candidates.

引用

页码：2435 / 2444

页数：10

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