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Open AccessArticle

Synthesis and Preliminary Biological Evaluation of Two Fluoroolefin Analogs of Largazole Inspired by the Structural Similarity of the Side Chain Unit in Psammaplin A

1
School of Pharmacy, Fudan University, 826 Zhangheng Road, Pudong Zone, Shanghai 201203, China
2
College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, China
3
Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
*
Author to whom correspondence should be addressed.
These authors contributed equally to the work.
Mar. Drugs 2019, 17(6), 333; https://doi.org/10.3390/md17060333
Received: 15 May 2019 / Revised: 27 May 2019 / Accepted: 28 May 2019 / Published: 3 June 2019
(This article belongs to the Special Issue Synthesis of marine natural products and analogues)
Largazole, isolated from a marine Cyanobacterium of the genus Symploca, is a potent and selective Class I HDAC (histone deacetylation enzymes) inhibitor. This natural 16-membered macrocyclic depsipeptide features an interesting side chain unit, namely 3-hydroxy-7-mercaptohept-4-enoic acid, which occurs in many other natural sulfur-containing HDAC inhibitors. Notably, one similar fragment, where the amide moiety replaces the trans alkene moiety, appears in Psammaplin A, another marine natural product with potent HDAC inhibitory activities. Inspired by such a structural similarity, we hypothesized the fluoroolefin moiety would mimic both the alkene moiety in Largazole and the amide moiety in Psammaplin A, and thus designed and synthesized two novel fluoro olefin analogs of Largazole. The preliminary biological assays showed that the fluoro analogs possessed comparable Class I HDAC inhibitory effects, indicating that this kind of modification on the side chain of Largazole was tolerable. View Full-Text
Keywords: marine natural product; Largazole; Psammaplin A; HDAC inhibitors; luoro olefin marine natural product; Largazole; Psammaplin A; HDAC inhibitors; luoro olefin
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MDPI and ACS Style

Zhang, B.; Shan, G.; Zheng, Y.; Yu, X.; Ruan, Z.-W.; Li, Y.; Lei, X. Synthesis and Preliminary Biological Evaluation of Two Fluoroolefin Analogs of Largazole Inspired by the Structural Similarity of the Side Chain Unit in Psammaplin A. Mar. Drugs 2019, 17, 333.

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