Spiroarborin, an ent-Clerodane Homodimer from Callicarpa arborea as an Inhibitor of the Eleven-Nineteen Leukemia (ENL) Protein by Targeting the YEATS Domain.

Abstract

A spiro ent-clerodane homodimer with a rare 6/6/6/6/6-fused pentacyclic scaffold, spiroarborin (1), together with four new monomeric analogues (2-5), were isolated from Callicarpa arborea. Their structures were elucidated by comprehensive spectroscopic data analysis, quantum-chemical calculations, and X-ray diffraction. A plausible biosynthetic pathway of 1 was proposed, and a biomimetic synthesis of its derivative was accomplished. Compound 1 showed a potent inhibitory effect by directly binding to the YEATS domain of the 11-19 leukemia (ENL) protein with an IC50 value of 7.3 μM. This gave a KD value of 5.0 μM, as recorded by a surface plasmon resonance binding assay.

• Authors: De-Bing Pu, Si-Qi Guo, Dong-Xuan Ni, Jing Lin, Jun-Bo Gao, Xiao-Ning Li, Rui-Han Zhang, Xiao-Li Li, Cheng Luo, Shi-Jie Chen, Wei-Lie Xiao
• Journal: Journal of natural products (J Nat Prod) Vol. 85 Issue 2 Pg. 317-326 (02 25 2022) ISSN: 1520-6025 [Electronic] United States
• PMID: 35029993 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Diterpenes, Clerodane
• Histones

Topics

• Callicarpa (chemistry)
• Diterpenes, Clerodane (chemistry, pharmacology)
• Histones (metabolism)
• Leukemia
• Molecular Structure
• Protein Domains