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Synthesis and biological evaluation of chromone derivatives against triple-negative breast cancer cells

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Abstract

This study described the bioactivity and the structure-activity relationship (SAR) of newly synthesized chromone derivatives against triple-negative breast cancer (TNBC) MDA-MB-231 cells. Among the compounds tested, C8 exerted a growth inhibitory effect on the TNBC-derived MDA-MB-231 cells with an IC50 value of 11.71 ± 0.79 µM. Results showed that it could promote apoptosis, sensitize TNBC MDA-MB-231 cells to doxorubicin (Dox) and inhibit multiple kinase activities with higher selectivity against PIM1 and PIM2 kinases. Molecular docking results revealed compound C8 engaged in several critical interactions with the important residues in PIM1 and PIM2 binding sites. This suggests that compound C8 possessed anticancer activity on TNBC cells potentially mediated by inhibition of multiple tyrosine kinases and kinases involved in cell-cycle regulation.

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Acknowledgements

This work was financially supported by GUP-2020-006 Universiti Kebangsaan Malaysia (UKM).

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Authors and Affiliations

  1. Centre for Drug and Herbal Development, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, 50300, Kuala Lumpur, Malaysia

    Rajibul Islam, Mock Phooi Yan & Lam Kok Wai

  2. Faculty Pharmacy and Health Sciences, Universiti Kuala Lumpur, Royal College of Medicine Perak, 30450, Ipoh, Perak, Malaysia

    Khor Poh Yen

  3. Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia

    Nurulfazlina Edayah Rasol

  4. Faculty of Applied Sciences, Universiti Teknologi MARA, 40450, Shah Alam, Selangor, Malaysia

    Nurulfazlina Edayah Rasol

  5. Center for Toxicology and Health Risk Studies, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300, Kuala Lumpur, Malaysia

    Chan Kok Meng

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  1. Rajibul Islam
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Islam, R., Yan, M.P., Yen, K.P. et al. Synthesis and biological evaluation of chromone derivatives against triple-negative breast cancer cells. Med Chem Res 32, 884–898 (2023). https://doi.org/10.1007/s00044-023-03048-4

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