Bioorganic & Medicinal Chemistry Letters 2013-02-01

Epidithiodiketopiperazine as a pharmacophore for protein lysine methyltransferase G9a inhibitors: reducing cytotoxicity by structural simplification.

Shinya Fujishiro, Kosuke Dodo, Eriko Iwasa, Yuou Teng, Yoshihiro Sohtome, Yoshitaka Hamashima, Akihiro Ito, Minoru Yoshida, Mikiko Sodeoka

文献索引：Bioorg. Med. Chem. Lett. 23(3) , 733-6, (2013)

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摘要

Chaetocin (1), a structurally complex epidithiodiketopiperazine (ETP) alkaloid produced by Chaetomium minutum, is a potent inhibitor of protein lysine methyltransferase G9a, which plays important roles in many biological processes. Here we present our synthetic investigations to identify a simple prototype G9a inhibitor structure based on structure-activity relationship (SAR) studies on chaetocin derivatives. The simple derivative PS-ETP-1 (14) was found to be a potent G9a inhibitor with greatly reduced cytotoxicity.Copyright © 2012 Elsevier Ltd. All rights reserved.