Borgini Matteo, Zamperini Claudio, Poggialini Federica, Ferrante Luca, Summa Vincenzo, Botta Maurizio, Fabio Romano Di
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy.
Lead Discovery Siena S.r.l., Castelnuovo Berardenga, 53019 Siena, Italy.
ACS Med Chem Lett. 2020 Feb 7;11(5):846-851. doi: 10.1021/acsmedchemlett.9b00643. eCollection 2020 May 14.
The marine natural product Largazole is the most potent Class I HDAC inhibitor identified to date. Since its discovery, many research groups have been attracted by the structural complexity and the peculiar anticancer activity, due to its capability to discriminate between tumor cells and normal cells. Herein, we discuss the synthesis and the biological profile of hybrid analogues of Largazole, as dual HDAC inhibitor and nitric oxide (NO) donors, potentially useful as anticancer agents. In particular, the metabolic stability of the modified thioester moiety of Largazole, bearing the NO-donor function/s, the release of NO, and the antiproliferative activity in tumor cell lines are presented.
海洋天然产物拉戈唑是迄今为止发现的最有效的I类组蛋白去乙酰化酶（HDAC）抑制剂。自其被发现以来，由于其能够区分肿瘤细胞和正常细胞，其结构复杂性和独特的抗癌活性吸引了许多研究团队。在此，我们讨论了作为双重HDAC抑制剂和一氧化氮（NO）供体的拉戈唑杂合类似物的合成及其生物学特性，这些类似物有可能用作抗癌药物。特别介绍了带有NO供体功能的拉戈唑修饰硫酯部分的代谢稳定性、NO的释放以及在肿瘤细胞系中的抗增殖活性。
