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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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
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author Lee, Szu
Chao, Min-Wu
Wu, Yi-Wen
Hsu, Chia-Min
Lin, Tony Eight
Hsu, Kai-Cheng
Pan, Shiow-Lin
Lee, Hsueh-Yun
author_facet Lee, Szu
Chao, Min-Wu
Wu, Yi-Wen
Hsu, Chia-Min
Lin, Tony Eight
Hsu, Kai-Cheng
Pan, Shiow-Lin
Lee, Hsueh-Yun
author_sort Lee, Szu
collection PubMed
description 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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spelling pubmed-106138532023-10-31 Synthesis and evaluation of potent (iso)ellipticine-based inhibitors of MYLK4 accessed via expeditious synthesis from isoquinolin-5-ol Lee, Szu Chao, Min-Wu Wu, Yi-Wen Hsu, Chia-Min Lin, Tony Eight Hsu, Kai-Cheng Pan, Shiow-Lin Lee, Hsueh-Yun RSC Adv Chemistry 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. The Royal Society of Chemistry 2023-10-30 /pmc/articles/PMC10613853/ /pubmed/37908644 http://dx.doi.org/10.1039/d3ra06600b Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Lee, Szu
Chao, Min-Wu
Wu, Yi-Wen
Hsu, Chia-Min
Lin, Tony Eight
Hsu, Kai-Cheng
Pan, Shiow-Lin
Lee, Hsueh-Yun
Synthesis and evaluation of potent (iso)ellipticine-based inhibitors of MYLK4 accessed via expeditious synthesis from isoquinolin-5-ol
title Synthesis and evaluation of potent (iso)ellipticine-based inhibitors of MYLK4 accessed via expeditious synthesis from isoquinolin-5-ol
title_full Synthesis and evaluation of potent (iso)ellipticine-based inhibitors of MYLK4 accessed via expeditious synthesis from isoquinolin-5-ol
title_fullStr Synthesis and evaluation of potent (iso)ellipticine-based inhibitors of MYLK4 accessed via expeditious synthesis from isoquinolin-5-ol
title_full_unstemmed Synthesis and evaluation of potent (iso)ellipticine-based inhibitors of MYLK4 accessed via expeditious synthesis from isoquinolin-5-ol
title_short Synthesis and evaluation of potent (iso)ellipticine-based inhibitors of MYLK4 accessed via expeditious synthesis from isoquinolin-5-ol
title_sort synthesis and evaluation of potent (iso)ellipticine-based inhibitors of mylk4 accessed via expeditious synthesis from isoquinolin-5-ol
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10613853/
https://www.ncbi.nlm.nih.gov/pubmed/37908644
http://dx.doi.org/10.1039/d3ra06600b
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