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Synthesis and antitumor evaluation of (aryl)methyl-amine derivatives of dehydroabietic acid-based B ring-fused-thiazole as potential PI3K/AKT/mTOR signaling pathway inhibitors

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Abstract

In an attempt to search for new natural product-based antitumor agents, a series of novel (aryl)methyl-amine derivatives of dehydroabietic acid-based B ring-fused-thiazole were designed and synthesized. The primary bioassay showed that compounds 5r and 5s presented certain inhibitory activity against cancer cells, weak cytotoxic activity against normal cells, and inhibitory activity against PI3K/AKT/mTOR signaling pathway. The binding modes and the binding site interactions between the active compounds and the target proteins were predicted preliminarily by the molecular docking method.

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Acknowledgements

This research was supported by Guangxi Natural Science Foundation under Grant Nos. 2018GXNSFAA138023 and 2019GXNSFAA245057, the Guangxi Distinguished Professor Grant (2018), Youth Science Foundation of Guangxi Medical University (No. GXMUYSF201703), and Open Research Project from Key Laboratory of High Incidence Diseases Prevention and Control of Guangxi Universities and Colleges, No. 02402214003-1705.

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Author notes

  1. Nai-Yuan Chen and Yu-Lan Xie have contributed equally to this work.

Authors and Affiliations

  1. School of Public Health, Guangxi Medical University, Nanning, 530021, China

    Nai-Yuan Chen, Yu-Lan Xie, Guo-Dong Lu, Yu-Wen Huang & Ming-Li Huang

  2. Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, 530021, China

    Nai-Yuan Chen, Yu-Lan Xie, Guo-Dong Lu, Xin-Yu Li, Yu-Wen Huang, Ming-Li Huang & Cui-Ping Li

  3. School of Preclinical Medicine, Guangxi Medical University, Nanning, 530021, China

    Fang Ye & Xin-Yu Li

  4. Pharmaceutical College, Guangxi Medical University, Nanning, 530021, China

    Tie-Yu Chen

  5. Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, Guangxi Key Laboratory of Oral and Maxillofacial Surgery Disease Treatment, Guangxi Clinical Research Center for Craniofacial Deformity, School of Stomatology, Guangxi Medical University, Nanning, 530021, China

    Cui-Ping Li

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Chen, NY., Xie, YL., Lu, GD. et al. Synthesis and antitumor evaluation of (aryl)methyl-amine derivatives of dehydroabietic acid-based B ring-fused-thiazole as potential PI3K/AKT/mTOR signaling pathway inhibitors. Mol Divers 25, 967–979 (2021). https://doi.org/10.1007/s11030-020-10081-7

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