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

Université Paris-Saclay
Institut Curie
Université PSL
CNRS UMR9187

Résultats de recherche: Contribution à un journal › Article › Revue par des pairs

18 Citations (Scopus)

Résumé

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.

langue originale	Anglais
Numéro d'article	114052
journal	European Journal of Medicinal Chemistry
Volume	229
Les DOIs	https://doi.org/10.1016/j.ejmech.2021.114052
état	Publié - 5 févr. 2022
Modification externe	Oui

SDG des Nations Unies

Ce résultat contribue à ou aux Objectifs de développement durable suivants

SDG 3 Bonne santé et bien-être

Accès au document

10.1016/j.ejmech.2021.114052

Contient cette citation

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

@article{e95fdcd3a72c400f974f97bb4d49da9d,

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{\textendash}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",

issn = "0223-5234",

publisher = "Elsevier Masson s.r.l.",

}

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

Résumé

SDG des Nations Unies

Accès au document

Empreinte digitale

Contient cette citation