Issue 45, 2023
From the journal:

RSC Advances

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

Szu Lee,‡a   Min-Wu Chao,‡bcd   Yi-Wen Wu,e   Chia-Min Hsu,e   Tony Eight Lin,ef   Kai-Cheng Hsu,efghi   Shiow-Lin Panefghi  and  Hsueh-Yun Lee ORCID logo *aij  

* Corresponding authors

a School of Pharmacy, College of Pharmacy, Taipei Medical University, Taiwan
E-mail: hyl@tmu.edu.tw
Tel: +886-2-7361661

b School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan

c Institute of Biopharmaceutical Sciences, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan

d The Doctoral Program of Clinical and Experimental Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan

e Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan

f PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan

g TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan

h TMU Research Center for Drug Discovery, Taipei Medical University, Taipei, Taiwan

i PhD Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, Taipei, Taiwan

j Master Program in Clinical Genomics and Proteomics, College of Pharmacy, Taipei Medical University, Taipei, Taiwan

Abstract

The K2S2O8-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 IC50 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.

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

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Article information

DOI
https://doi.org/10.1039/D3RA06600B
Article type
Paper
Submitted
27 Sep 2023
Accepted
23 Oct 2023
First published
30 Oct 2023
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2023,13, 31595-31601

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

S. Lee, M. Chao, Y. Wu, C. Hsu, T. E. Lin, K. Hsu, S. Pan and H. Lee, RSC Adv., 2023, 13, 31595 DOI: 10.1039/D3RA06600B

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