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ID: ALA5136984

Journal: Eur J Med Chem

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

Authors: Mathieu C, Chamayou Q, Hyen Luong TT, Naud D, Mahuteau-Betzer F, Alami M, Fattal E, Messaoudi S, Vergnaud-Gauduchon J.

Abstract: A series of 6BrCaQ-Cn-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 GI50 values at a nanomolar level in a diverse set of human cancer cells (GI50 = 0.008-0.30 μM) including MDA-MB231, HT-29, HCT-116, K562, and PC-3 cancer cell lines. Moreover, the best lead compound 6BrCaQ-C10-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.

CiteXplore: 34952432

DOI: 10.1016/j.ejmech.2021.114052