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. 2025 Sep 10.
doi: 10.1007/s11030-025-11353-w. Online ahead of print.

Design and synthesis of novel indolinone Aurora B kinase inhibitors based on fragment-based drug discovery (FBDD)

Baoxing Xie  1   2 , Miaomiao Shi  1   2 , Dan Tang  1 , Shan Yang  1 , Yan Zeng  3 , Lifei Nie  1 , Chao Niu  4   5
Affiliations

Design and synthesis of novel indolinone Aurora B kinase inhibitors based on fragment-based drug discovery (FBDD)

Baoxing Xie et al. Mol Divers. .

Abstract

Aurora kinases are a group of serine/threonine kinases essential for cell mitosis, comprising Aurora A, B, and C. However, the Aurora B is overexpressed in multiple tumors and the aurone has been proved to exhibit potent inhibitory activity against Aurora B kinase by our group. The indolinone was considered as an aurone scaffold hopping analog, and the indolinone-based Aurora B inhibitor library (3577 molecules) was constructed by FBDD strategy. After pharmacophore model and molecular docking, the candidate molecules were identified, then synthesized via Suzuki-Miyaura and Knoevenagel reactions. The compounds 3-17a, 3-17d and 3-17 k especially inhibited Aurora B in the nanomolar range (IC50 = 1.100, 1.518 and 0.8911 nM, respectively), showing no significant inhibition of Aurora A. Notably, the most potent 3-17 k demonstrated the strongest antiproliferative activity against HGC27 (IC50 = 2.05 μM) and HT-29 (IC50 = 2.07 μM) cell lines, as well as Aurora B over-expression cells, including OVCAR8 (IC50 = 3.02 μM), T24 (IC50 = 10.21 μM), NCIH1299 (IC50 = 7.32 μM) and SW480 (IC50 = 4.45 μM), while maintaining a lower cytotoxicity in normal human cells (GES-1 and NCM460). Additionally, molecular dynamics simulation were conducted to explore the binding interactions between 3-17 k and Aurora B (PDB: 5EYK), revealing favorable binding free energy (-33.34 kcal·mol-1). Based on available data, compound 3-17 k warrants comprehensive investigation to evaluate its potential as an anticancer drug candidate.

Keywords: Aurora B; FBDD; Indolinone derivatives; Pharmacophore; Tumor.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no competing interests.

References

    1. Boucherle B, Peuchmaur M, Boumendjel A, Haudecoeur R (2017) Occurrences, biosynthesis and properties of aurones as high-end evolutionary products. Phytochemistry 142:92–111. https://doi.org/10.1016/j.phytochem.2017.06.017 - DOI - PubMed
    1. Li JQ, Xiao CJ, Li YM, Tian XY, Dong X, Jiang B (2020) Astrernestin, a novel aurone-phenylpropanoid adduct from the roots of Astragalus ernestii. Nat Prod Res 34:2894–2899. https://doi.org/10.1080/14786419.2019.1596101 - DOI - PubMed
    1. Alsayari A, Muhsinah AB, Hassan MZ, Ahsan MJ, Alshehri JA, Begum N (2019) Aurone: a biologically attractive scaffold as anticancer agent. Eur J Med Chem 166:417–431. https://doi.org/10.1016/j.ejmech.2019.01.078 - DOI - PubMed
    1. Dokla EME, Abdel-Aziz AK, Milik SN, Mahmoud AH, Saadeldin MK, McPhillie MJ, Minucci S, Abouzid KAM (2021) Indolin-2-one derivatives as selective Aurora B kinase inhibitors targeting breast cancer. Bioorg Chem 117:105451. https://doi.org/10.1016/j.bioorg.2021.105451 - DOI - PubMed
    1. Wu H, Zhao H, Lu T, Xie B, Niu C, Aisa HA (2023) Synthesis and activity of aurone and indanone derivatives. Med Chem 19:686–703. https://doi.org/10.2174/1573406419666230203105246 - DOI - PubMed

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