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

被引：3

作者：

Islam, Rajibul ^{[1
]}

Yan, Mock Phooi ^{[1
]}

Yen, Khor Poh ^{[2
]}

Rasol, Nurulfazlina Edayah ^{[3
,4
]}

Meng, Chan Kok ^{[5
]}

Wai, Lam Kok ^{[1
]}

机构：

[1] Univ Kebangsaan Malaysia, Fac Pharm, Ctr Drug & Herbal Dev, Kuala Lumpur 50300, Malaysia

[2] Univ Kuala Lumpur, Royal Coll Med Perak, Fac Pharm & Hlth Sci, Ipoh 30450, Perak, Malaysia

[3] Univ Teknol MARA, Atta ur Rahman Inst Nat Prod Discovery, Puncak Alam Campus, Bandar Puncak Alam 42300, Selangor, Malaysia

[4] Univ Teknol MARA, Fac Appl Sci, Shah Alam 40450, Selangor, Malaysia

[5] Univ Kebangsaan Malaysia, Fac Hlth Sci, Ctr Toxicol & Hlth Risk Studies, Jalan Raja MudaAbdul Aziz, Kuala Lumpur 50300, Malaysia

来源：

MEDICINAL CHEMISTRY RESEARCH | 2023年 / 32卷 / 05期

关键词：

Triple-negative breast cancer; Chromone; Anticancer; Multi-kinase inhibitor; INHIBITOR LY294002; KINASE; DOXORUBICIN; DESIGN; DEATH; PROLIFERATION; OPTIMIZATION; CHEMOTHERAPY; EXPRESSION; EFFICIENT;

D O I：

10.1007/s00044-023-03048-4

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 mu M. 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.

引用

页码：884 / 898

页数：15

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