Department of Chemistry, Duke University, Durham, NC 27708, USA.
Nat Prod Rep. 2012 Apr;29(4):449-56. doi: 10.1039/c2np00066k. Epub 2012 Feb 14.
The cyclic depsipeptide largazole from a cyanobacterium of the genus Symploca is a marine natural product with a novel chemical scaffold and potently inhibits class I histone deacetylases (HDACs). Largazole possesses highly differential growth-inhibitory activity, preferentially targeting transformed over non-transformed cells. The intriguing structure and biological activity of largazole have attracted strong interest from the synthetic chemistry community to establish synthetic routes to largazole and to investigate its potential as a cancer therapeutic. This Highlight surveys recent advances in this area with a focus on the discovery, synthesis, target identification, structure-activity relationships, HDAC8-largazole thiol crystal structure, and biological studies, including in vivo anticancer and osteogenic activities.
来自 Symploca 属蓝藻的环二肽 largazole 是一种具有新颖化学支架的海洋天然产物，能够强烈抑制 I 类组蛋白去乙酰化酶（HDACs）。 largazole 具有高度差异化的生长抑制活性，优先靶向转化细胞而非非转化细胞。 largazole 引人入胜的结构和生物活性引起了合成化学界的浓厚兴趣，他们致力于建立 largazole 的合成途径，并研究其作为癌症治疗药物的潜力。本文重点介绍了该领域的最新进展，包括 largazole 的发现、合成、靶标鉴定、构效关系、HDAC8-largazole 巯基晶体结构以及体内抗癌和成骨活性等生物研究。
