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

Clelia Mathieu; Quentin Chamayou; Thi Thanh Hyen Luong; Delphine Naud; Florence Mahuteau-Betzer; Mouad Alami; Elias Fattal; Samir Messaoudi; Juliette Vergnaud-Gauduchon

doi:10.1016/j.ejmech.2021.114052

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

Clelia Mathieu
, Quentin Chamayou
, Thi Thanh Hyen Luong
, Delphine Naud
, Florence Mahuteau-Betzer
, Mouad Alami
, Elias Fattal
, Samir Messaoudi
, Juliette Vergnaud-Gauduchon

Research output: Contribution to journal › Article › peer-review

Abstract

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 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.

Original language	English
Article number	114052
Journal	European Journal of Medicinal Chemistry
Volume	229
DOIs	https://doi.org/10.1016/j.ejmech.2021.114052
Publication status	Published - 5 Feb 2022
Externally published	Yes

Keywords

6BrCaQ
Anti-Proliferative activity
HSP90
Mitochondrial targeting
TRAP1
Triphenylphosphonium TPP

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ejmech.2021.114052

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Mathieu, C., Chamayou, Q., Hyen Luong, T. T., Naud, D., Mahuteau-Betzer, F., Alami, M., Fattal, E., Messaoudi, S., & Vergnaud-Gauduchon, J. (2022). Synthesis and antiproliferative activity of 6BrCaQ-TPP conjugates for targeting the mitochondrial heat shock protein TRAP1. European Journal of Medicinal Chemistry, 229, Article 114052. https://doi.org/10.1016/j.ejmech.2021.114052

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

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.",

keywords = "6BrCaQ, Anti-Proliferative activity, HSP90, Mitochondrial targeting, TRAP1, Triphenylphosphonium TPP",

author = "Clelia Mathieu and Quentin Chamayou and \{Hyen Luong\}, \{Thi Thanh\} and Delphine Naud and Florence Mahuteau-Betzer and Mouad Alami and Elias Fattal and Samir Messaoudi and Juliette Vergnaud-Gauduchon",

note = "Publisher Copyright: {\textcopyright} 2021",

year = "2022",

month = feb,

day = "5",

doi = "10.1016/j.ejmech.2021.114052",

language = "English",

volume = "229",

journal = "European Journal of Medicinal Chemistry",

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TY - JOUR

T1 - Synthesis and antiproliferative activity of 6BrCaQ-TPP conjugates for targeting the mitochondrial heat shock protein TRAP1

AU - Mathieu, Clelia

AU - Chamayou, Quentin

AU - Hyen Luong, Thi Thanh

AU - Naud, Delphine

AU - Mahuteau-Betzer, Florence

AU - Alami, Mouad

AU - Fattal, Elias

AU - Messaoudi, Samir

AU - Vergnaud-Gauduchon, Juliette

PY - 2022/2/5

Y1 - 2022/2/5

N2 - 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.

AB - 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.

KW - 6BrCaQ

KW - Anti-Proliferative activity

KW - HSP90

KW - Mitochondrial targeting

KW - TRAP1

KW - Triphenylphosphonium TPP

U2 - 10.1016/j.ejmech.2021.114052

DO - 10.1016/j.ejmech.2021.114052

M3 - Article

C2 - 34952432

AN - SCOPUS:85121432296

SN - 0223-5234

VL - 229

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

M1 - 114052

ER -

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

Abstract

Keywords

UN SDGs

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