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Semi-synthesis and in vitro anti-cancer effects evaluation of novel xanthohumol derivatives

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Abstract

Xanthohumol (Xn) is a chalcone compound isolated from Humulus lupulus Linn., that has various biological activities. In this study, eight Xn derivatives were synthesized by Williamson, Mannich, Reimer-Tiemann, and Schiff base reactions, and evaluated for their in vitro cytotoxic activity against five human cancer cell lines (MDA-MB-231, MCF-7, CNE-2Z, SMMC-7721, and H1975). Among these compounds, 2-((E)-2,4-dihydroxy-5-((E)-3-(4-hydroxyphenyl)acryloyl)-6-methoxy-3-(3- methylbut-2-en-1-yl)benzylidene)hydrazine-1-carboximidamide (8) exhibited the most potent cytotoxic activity against the five cancer cells, with IC50 values ranging from 4.87 to 14.35 µM. Wound-healing and transwell assays showed that compound 8 inhibited the migration and invasion of MDA-MB-231 cells by down-regulation HIF-1α, MMP-2 and MMP-9 protein expression. We further demonstrated that compound 8 induced apoptosis of MDA-MB-231 cells by increasing of Bax/Bcl-2 ratio and down-regulation of Akt protein expression.

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Acknowledgements

This work was financially supported by the Anhui Provincial Natural Science Foundation (2008085MH284); 512 Talent Cultivation Plan of Bengbu Medical College (By51202202); Anhui Engineering Technology Research Center of Biochemical Pharmaceutical Foundation (2022SYKFZ03).

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Authors and Affiliations

  1. School of Pharmacy, Bengbu Medical College, 2600 Donghai Road, Bengbu, Anhui, 233030, China

    Xiaolong Sun, Jie Chen, Di Huang, Feng Ding, Long Zhao, Hong-Mei Li & Cheng-Zhu Wu

  2. Anhui Province Engineering Technology Research Center of Biochemical Pharmaceutical, Bengbu, Anhui, 233030, China

    Feng Ding, Long Zhao, Hong-Mei Li, Yu-Xin Zhang & Cheng-Zhu Wu

  3. School of Laboratory Medicine, Bengbu Medical College, 2600 Donghai Road, Bengbu, Anhui, 233030, China

    Xiang-Shu Wang & Yu-Xin Zhang

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  1. Xiaolong Sun
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Contributions

Conceptualization, C.-Z.W. and Y.-X.Z.; methodology, X.-L.S., J.C.; software, F.D. and L.Z.; investigation, J.C. and X.-S. W.; formal analysis, L.Z.; data curation, F.D.; writing—original draft preparation, X.-L.S. and H.-M.L.; writing—review and editing, X.-S. W. and H.-M.L.; supervision, C.-Z.W., and Y.-X.Z.; project administration, C.-Z.W. and X.-L.S.; funding acquisition, C.-Z.W. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Yu-Xin Zhang or Cheng-Zhu Wu.

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Sun, X., Chen, J., Huang, D. et al. Semi-synthesis and in vitro anti-cancer effects evaluation of novel xanthohumol derivatives. Mol Divers (2023). https://doi.org/10.1007/s11030-023-10706-7

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