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Discovery of α-methylene-γ-lactone-δ-epoxy derivatives with anti-cancer activity: synthesis, SAR study, and biological activity

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Abstract

A series of new Parthenolide analogs (4a-4k) were designed and synthesized. It was known that most of the compounds showed antiproliferative activities against the six cancer cell lines including DU-145, Hela, HepG2, MCF-7, SGC-7901 and K562 by evaluating their biological activities. Among them, compound 4f exhibited better cell proliferative inhibition against the tested cell lines. In addition, anticancer mechanism studies illustrated that compound 4f could induce apoptosis in MCF-7/ADR cells via PI3K/Akt, MAPKs pathway and caspase-dependent mitochondrial pathway. More importantly, compound 4f induced an increase of autophagy levels in MCF-7/ADR cells. It was found that compared with the lead compound Parthenolide, compound 4f showed more significant anticancer effects. Our research provided an efficient strategy for targeting anticancer drug development.

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Acknowledgements

This work was supported by the Postgraduate Research & Practice Innovation Program of Jiangsu Province (Grant No. SJCX21_1294).

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Authors and Affiliations

  1. School of Pharmacy, Changzhou University, 1 Gehu Road, Wujin district, Changzhou, 213164, Jiangsu, PR China

    Jie Ren, Pengchao Yu, Meiju Zhang, Yuexin Zhao, Jian Zhong & Kun Hu

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  1. Jie Ren
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  2. Pengchao Yu
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Ren, J., Yu, P., Zhang, M. et al. Discovery of α-methylene-γ-lactone-δ-epoxy derivatives with anti-cancer activity: synthesis, SAR study, and biological activity. Med Chem Res 31, 1803–1817 (2022). https://doi.org/10.1007/s00044-022-02925-8

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