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Design, synthesis, and anti-breast tumor activity of novel combretastatin A-4 analogues

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Abstract

We reported the design, synthesis, and biological evaluation of 9 novel benzofuran analogues of CA-4 and their preliminary structure-activity relationship with inhibitory activity on microtubules and the phosphoinositide 3-kinase (PI3K). Various spectroscopic techniques like 1H NMR, 13C NMR, and HRMS were used for characterization of all synthesized analogs. Among these derivatives, most compounds inhibited the growth of breast tumor cell lines, especially one compound showed prominently inhibitory activity in MCF-7 and MDA-MB-231 cells with IC50 value as 3.88 and 5.78 μmol/dm3. Furthermore, we found that the same compound reduced the PI3K expression levels, conversely elevated the β-tubulin expression levels in enzyme-linked immunosorbent assay. The binding interactions between synthesized analogs and colchicine active site of tubulin protein and the PI3Kα protein were confirmed through molecular docking study. These preliminary results showed that this compound has the potency for further study as a dual-target anti-tumor inhibitor.

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The data are available from the corresponding author on reasonable request.

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Acknowledgements

The study was supported by Natural Science Foundation of Xinjiang Uygur Autonomous Region (No.2021D01F40) and Xinjiang Second Medical College Research Fund General Project (No.MS202301). We thank it for the financial support given to the research projects.

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Authors and Affiliations

  1. School of Pharmacy, Xinjiang Second Medical College, Karamay, 834000, China

    Yiting Gao & Jinfang Li

  2. Department of Physical Education, Xinjiang Second Medical College, Karamay, 834000, XinJiang, China

    Teng Ma

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  1. Yiting Gao
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  2. Jinfang Li
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  3. Teng Ma
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Correspondence to Yiting Gao.

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Gao, Y., Li, J. & Ma, T. Design, synthesis, and anti-breast tumor activity of novel combretastatin A-4 analogues. Monatsh Chem 154, 1285–1294 (2023). https://doi.org/10.1007/s00706-023-03127-7

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  • DOI: https://doi.org/10.1007/s00706-023-03127-7

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