Synthesis and evaluation of potent (iso)ellipticine-based inhibitors of MYLK4 accessed via expeditious synthesis from isoquinolin-5-ol

The K(2)S(2)O(8)-mediated generation of p-iminoquinone contributed to the regioselective substitution of isoquinolin-5,8-dione. This hydroxyl group-guided substitution was also applied to selected heterocycles and addressed the regioselectivity issue of quinones. This study has provided an expeditio...

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Detalles Bibliográficos
Autores principales: Lee, Szu, Chao, Min-Wu, Wu, Yi-Wen, Hsu, Chia-Min, Lin, Tony Eight, Hsu, Kai-Cheng, Pan, Shiow-Lin, Lee, Hsueh-Yun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2023
Materias:
Chemistry
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10613853/
https://www.ncbi.nlm.nih.gov/pubmed/37908644
http://dx.doi.org/10.1039/d3ra06600b
Descripción
Sumario:The K(2)S(2)O(8)-mediated generation of p-iminoquinone contributed to the regioselective substitution of isoquinolin-5,8-dione. This hydroxyl group-guided substitution was also applied to selected heterocycles and addressed the regioselectivity issue of quinones. This study has provided an expeditious pathway from isoquinolin-5-ol (5) to ellipticine (1) and isoellipticine (2), which benefits the comprehensive comparison of their activity. Compounds 1 and 2 displayed marked MYLK4 inhibitory activity with IC(50) values of 7.1 and 6.1 nM, respectively. In the cellular activity of AML cells (MV-4-11 and MOLM-13), compound 1 showed better AML activity than compound 2.

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