Synthesis and antiproliferative activity of 6BrCaQ-TPP conjugates for targeting the mitochondrial heat shock protein TRAP1

被引：9

作者：

Mathieu, Clelia ^{[1
]}

Chamayou, Quentin ^{[2
]}

Luong, Thi Thanh Hyen ^{[2
]}

Naud, Delphine ^{[3
,4
]}

Mahuteau-Betzer, Florence ^{[3
,4
]}

Alami, Mouad ^{[2
]}

Fattal, Elias ^{[1
]}

Messaoudi, Samir ^{[2
]}

Vergnaud-Gauduchon, Juliette ^{[1
]}

机构：

[1] Univ Paris Saclay, CNRS, Inst Galien Paris Saclay, F-92296 Chatenay Malabry, France

[2] Univ Paris Saclay, CNRS, BioCIS, F-92290 Chatenay Malabry, Malabry, France

[3] Univ PSL, CNRS, Chem & Modeling Biol Canc, INSERM,Inst Curie,U1196,UMR9187, F-91400 Orsay, France

[4] Univ Paris Saclay, CNRS, Chem & Modeling Biol Canc, INSERM,U1196,UMR9187, F-91400 Orsay, France

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2022年 / 229卷

关键词：

TRAP1; 6BrCaQ; HSP90; Triphenylphosphonium TPP; Mitochondrial targeting; Anti-Proliferative activity; HSP90; INHIBITOR; CANCER-CELLS; CHAPERONE; METABOLISM; SYNTHASE; INDUCE; CYCLE;

D O I：

10.1016/j.ejmech.2021.114052

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 6BrCaQ-C-n-TPP conjugates 3a-f and 5 was designed and synthesized as a novel class of TRAP1 inhibitors. Compound 3a displayed an excellent anti-proliferative activity with mean GI(50) values at a nanomolar level in a diverse set of human cancer cells (GI(50) =& nbsp;0.008-0.30 mu M) including MDA-MB231, HT-29, HCT-116, K562, and PC-3 cancer cell lines. Moreover, the best lead compound 6BrCaQ-C-10-TPP induces a significant mitochondrial membrane disturbance combined to a regulation of HSP and partner protein levels as a first evidence that his mechanism of action involves the TRAP-1 mitochondrial Hsp90 machinery. (c) 2021 Elsevier Masson SAS. All rights reserved.

引用

页数：13

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