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Design, Synthesis, Biological Evaluation, and Molecular Docking Studies of Indazole Derivatives as Bcl-2/Mcl-1 Dual Inhibitors

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Abstract

In this study, a series of new indazole derivatives has been designed, synthesized and evaluated for inhibitory activity against anti-apoptotic Bcl-2 proteins (Bcl-2, Mcl-1, Bcl-xL). Among them, three products have demonstrated high inhibitory activity against Bcl-2/Mcl-1, which is similar to that of the positive control compound WL-276. Their poor Bcl-xL inhibitory activity allows to avoid platelet toxicity caused by Bcl-xL inhibition. Hence, they might be considered as lead compounds for developing Bcl-2/Mcl-1 dual inhibitors of higher potency.

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Funding

This work was supported by National Natural Science Foundation of China (Grant no. 82003602, 21877034), The science and technology innovation Program of Hunan Province (Grant no. 2021RC5028), Scientific Research Fund of Hunan Provincial Education Department (Grant no. 21B0478) , Student Research and Innovation Program of Hunan University of Science and Technology (Grant no. YZ2141), and Open Project Program of Key Laboratory of Theoretical Organic Chemistry and Functional Molecule, Ministry of Education (Grant no. LKF202105).

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Authors and Affiliations

  1. Key Laboratory of Theoretical Organic Chemistry and Functional Molecule, Ministry of Education, School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, 411201, Hunan, China

    Xi Luo, Xu Deng, Jingyi Ruan, Wenyan Wang & Yichao Wan

  2. Hunan Provincial Key Laboratory of Controllable Preparation and Functional Application of Fine Polymers, Hunan Provincial Key Lab of Advanced Materials for New Energy Storage and Conversion, Hunan University of Science and Technology, Xiangtan, 411201, Hunan, China

    Yichao Wan

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  1. Xi Luo
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  2. Xu Deng
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Correspondence to Yichao Wan.

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Luo, X., Deng, X., Ruan, J. et al. Design, Synthesis, Biological Evaluation, and Molecular Docking Studies of Indazole Derivatives as Bcl-2/Mcl-1 Dual Inhibitors. Russ J Gen Chem 92, 1109–1114 (2022). https://doi.org/10.1134/S1070363222060238

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