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

• Published in: Medicinal Chemistry Research
• Main Author: Islam R.; Yan M.P.; Yen K.P.; Rasol N.E.; Meng C.K.; Wai L.K.
• Format: Article
• Language: English
• Published: Springer 2023
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85150307123&doi=10.1007%2fs00044-023-03048-4&partnerID=40&md5=81802d76a55467947e7bbaa52f7759ba

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. © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.