螺旋 Arborin，一种来自 的 -Clerodane 同二聚体，通过靶向 YEATS 结构域抑制十一十九白血病 (ENL) 蛋白。
Spiroarborin, an -Clerodane Homodimer from as an Inhibitor of the Eleven-Nineteen Leukemia (ENL) Protein by Targeting the YEATS Domain.
机构信息
Key Laboratory of Medicinal Chemistry for Natural Resources, Ministry of Education, Yunnan Research & Development Center for Natural Products, School of Chemical Science and Technology, Yunnan University, Kunming 650091, People's Republic of China.
The Center for Chemical Biology, Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China.
出版信息
J Nat Prod. 2022 Feb 25;85(2):317-326. doi: 10.1021/acs.jnatprod.1c00775. Epub 2022 Jan 14.
A spiro -clerodane homodimer with a rare 6/6/6/6/6-fused pentacyclic scaffold, spiroarborin (), together with four new monomeric analogues (-), were isolated from . Their structures were elucidated by comprehensive spectroscopic data analysis, quantum-chemical calculations, and X-ray diffraction. A plausible biosynthetic pathway of was proposed, and a biomimetic synthesis of its derivative was accomplished. Compound showed a potent inhibitory effect by directly binding to the YEATS domain of the 11-19 leukemia (ENL) protein with an IC value of 7.3 μM. This gave a value of 5.0 μM, as recorded by a surface plasmon resonance binding assay.
从 中分离得到一个具有罕见的 6/6/6/6/6-稠合五环骨架的螺环- clerodane 二聚体螺 Arborin ()，以及四个新的单体类似物 (-)。通过综合光谱数据分析、量子化学计算和 X 射线衍射确定了它们的结构。提出了 的可能生物合成途径，并完成了其衍生物的仿生合成。化合物 对 YEATS 结构域具有很强的抑制作用，直接与 11-19 白血病（ENL）蛋白的 YEATS 结构域结合，IC 值为 7.3 μM。这给出了一个 5.0 μM 的 值，这是通过表面等离子体共振结合测定记录的。
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