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Updated: May 31, 2025

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Synthesis, Structural Modification, and Antismall Cell Lung Cancer Activity of 3-Arylisoquinolines with Dual
Xuemei Deng1,2,3,4, Yuying Wang1,2,3,4, Xiongqi Yang1,2,3,4
1Department of Respiratory and Critical Care Medicine, Molecularly Targeted Research and Development Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China.
Abstract:
To overcome the compensatory effect between Topo I and II, one of the reasons accounting for the resistance of SCLC patients, we are pioneering the use of 3-arylisoquinolines to develop dual inhibitors of Topo I/II for the management of SCLC. A total of 46 new compounds were synthesized. Compounds 3g (IC50 = 1.30 μM for NCI-H446 cells and 1.42 μM for NCI-H1048 cells) and 3x (IC50 = 1.32 μM for NCI-H446 cells and 2.45 μM for NCI-H1048 cells) were selected for detailed pharmacological investigation, due to their outstanding cytotoxicity and dual Topo I and II inhibitory activity. 3g and 3x effectively prevent SCLC cell proliferation, invasion, and migration in vitro, byinducing mitochondrial apoptosis and inhibiting the PI3K/Akt/mTOR pathway. Their in vivo tumor inhibition rate is comparable to etoposide with lower toxicity. These results indicated their potential therapeutic values as dual Topo I and II inhibitors for treating SCLC.
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