Dibenzofuran derivatives inspired from cercosporamide as dual inhibitors of pim and CLK1 kinases

Viet Hung Dao; Isabelle Ourliac-Garnier; Cédric Logé; Florence O. McCarthy; Stéphane Bach; Teresinha Gonçalves da Silva; Caroline Denevault-Sabourin; Jérôme Thiéfaine; Blandine Baratte; Thomas Robert; Fabrice Gouilleux; Marie Brachet-Botineau; Marc Antoine Bazin; Pascal Marchand

doi:10.3390/molecules26216572

Dibenzofuran derivatives inspired from cercosporamide as dual inhibitors of pim and CLK1 kinases

Viet Hung Dao
, Isabelle Ourliac-Garnier
, Cédric Logé
, Florence O. McCarthy
, Stéphane Bach
, Teresinha Gonçalves da Silva
, Caroline Denevault-Sabourin
, Jérôme Thiéfaine
, Blandine Baratte
, Thomas Robert
, Fabrice Gouilleux
, Marie Brachet-Botineau
, Marc Antoine Bazin
, Pascal Marchand

School of Chemistry

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

Abstract

Pim kinases (proviral integration site for Moloney murine leukemia virus kinases) are overexpressed in various types of hematological malignancies and solid carcinomas, and promote cell proliferation and survival. Thus, Pim kinases are validated as targets for antitumor therapy. In this context, our combined efforts in natural product-inspired library generation and screening furnished very promising dibenzo[b, d]furan derivatives derived from cercosporamide. Among them, lead compound 44 was highlighted as a potent Pim-1/2 kinases inhibitor with an additional nanomolar IC₅₀ value against CLK1 (cdc2-like kinases 1) and displayed a low micromolar anticancer potency towards the MV4-11 (AML) cell line, expressing high endogenous levels of Pim-1/2 kinases. The design, synthesis, structure-activity relationship, and docking studies are reported herein and supported by enzyme, cellular assays, and Galleria mellonella larvae testing for acute toxicity.

Original language	English
Article number	6572
Journal	Molecules
Volume	26
Issue number	21
DOIs	https://doi.org/10.3390/molecules26216572
Publication status	Published - 1 Nov 2021

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

Anticancer agents
Cercosporamide
CLK1 kinase
Dibenzo[b, d]furan
Kinase inhibitors
Pim kinases

Access to Document

10.3390/molecules26216572

Cite this

Dao, V. H., Ourliac-Garnier, I., Logé, C., McCarthy, F. O., Bach, S., da Silva, T. G., Denevault-Sabourin, C., Thiéfaine, J., Baratte, B., Robert, T., Gouilleux, F., Brachet-Botineau, M., Bazin, M. A., & Marchand, P. (2021). Dibenzofuran derivatives inspired from cercosporamide as dual inhibitors of pim and CLK1 kinases. Molecules, 26(21), Article 6572. https://doi.org/10.3390/molecules26216572

@article{870d11c82a7946a3a2a2abc4693c3daf,

title = "Dibenzofuran derivatives inspired from cercosporamide as dual inhibitors of pim and CLK1 kinases",

abstract = "Pim kinases (proviral integration site for Moloney murine leukemia virus kinases) are overexpressed in various types of hematological malignancies and solid carcinomas, and promote cell proliferation and survival. Thus, Pim kinases are validated as targets for antitumor therapy. In this context, our combined efforts in natural product-inspired library generation and screening furnished very promising dibenzo[b, d]furan derivatives derived from cercosporamide. Among them, lead compound 44 was highlighted as a potent Pim-1/2 kinases inhibitor with an additional nanomolar IC50 value against CLK1 (cdc2-like kinases 1) and displayed a low micromolar anticancer potency towards the MV4-11 (AML) cell line, expressing high endogenous levels of Pim-1/2 kinases. The design, synthesis, structure-activity relationship, and docking studies are reported herein and supported by enzyme, cellular assays, and Galleria mellonella larvae testing for acute toxicity.",

keywords = "Anticancer agents, Cercosporamide, CLK1 kinase, Dibenzo[b, d]furan, Kinase inhibitors, Pim kinases",

author = "Dao, \{Viet Hung\} and Isabelle Ourliac-Garnier and C{\'e}dric Log{\'e} and McCarthy, \{Florence O.\} and St{\'e}phane Bach and \{da Silva\}, \{Teresinha Gon{\c c}alves\} and Caroline Denevault-Sabourin and J{\'e}r{\^o}me Thi{\'e}faine and Blandine Baratte and Thomas Robert and Fabrice Gouilleux and Marie Brachet-Botineau and Bazin, \{Marc Antoine\} and Pascal Marchand",

note = "Publisher Copyright: {\textcopyright} 2021 by the authors.",

year = "2021",

month = nov,

day = "1",

doi = "10.3390/molecules26216572",

language = "English",

volume = "26",

journal = "Molecules",

issn = "1420-3049",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "21",

}

Dao, VH, Ourliac-Garnier, I, Logé, C, McCarthy, FO, Bach, S, da Silva, TG, Denevault-Sabourin, C, Thiéfaine, J, Baratte, B, Robert, T, Gouilleux, F, Brachet-Botineau, M, Bazin, MA & Marchand, P 2021, 'Dibenzofuran derivatives inspired from cercosporamide as dual inhibitors of pim and CLK1 kinases', Molecules, vol. 26, no. 21, 6572. https://doi.org/10.3390/molecules26216572

TY - JOUR

T1 - Dibenzofuran derivatives inspired from cercosporamide as dual inhibitors of pim and CLK1 kinases

AU - Dao, Viet Hung

AU - Ourliac-Garnier, Isabelle

AU - Logé, Cédric

AU - McCarthy, Florence O.

AU - Bach, Stéphane

AU - da Silva, Teresinha Gonçalves

AU - Denevault-Sabourin, Caroline

AU - Thiéfaine, Jérôme

AU - Baratte, Blandine

AU - Robert, Thomas

AU - Gouilleux, Fabrice

AU - Brachet-Botineau, Marie

AU - Bazin, Marc Antoine

AU - Marchand, Pascal

PY - 2021/11/1

Y1 - 2021/11/1

N2 - Pim kinases (proviral integration site for Moloney murine leukemia virus kinases) are overexpressed in various types of hematological malignancies and solid carcinomas, and promote cell proliferation and survival. Thus, Pim kinases are validated as targets for antitumor therapy. In this context, our combined efforts in natural product-inspired library generation and screening furnished very promising dibenzo[b, d]furan derivatives derived from cercosporamide. Among them, lead compound 44 was highlighted as a potent Pim-1/2 kinases inhibitor with an additional nanomolar IC50 value against CLK1 (cdc2-like kinases 1) and displayed a low micromolar anticancer potency towards the MV4-11 (AML) cell line, expressing high endogenous levels of Pim-1/2 kinases. The design, synthesis, structure-activity relationship, and docking studies are reported herein and supported by enzyme, cellular assays, and Galleria mellonella larvae testing for acute toxicity.

AB - Pim kinases (proviral integration site for Moloney murine leukemia virus kinases) are overexpressed in various types of hematological malignancies and solid carcinomas, and promote cell proliferation and survival. Thus, Pim kinases are validated as targets for antitumor therapy. In this context, our combined efforts in natural product-inspired library generation and screening furnished very promising dibenzo[b, d]furan derivatives derived from cercosporamide. Among them, lead compound 44 was highlighted as a potent Pim-1/2 kinases inhibitor with an additional nanomolar IC50 value against CLK1 (cdc2-like kinases 1) and displayed a low micromolar anticancer potency towards the MV4-11 (AML) cell line, expressing high endogenous levels of Pim-1/2 kinases. The design, synthesis, structure-activity relationship, and docking studies are reported herein and supported by enzyme, cellular assays, and Galleria mellonella larvae testing for acute toxicity.

KW - Anticancer agents

KW - Cercosporamide

KW - CLK1 kinase

KW - Dibenzo[b, d]furan

KW - Kinase inhibitors

KW - Pim kinases

UR - https://www.scopus.com/pages/publications/85120671229

U2 - 10.3390/molecules26216572

DO - 10.3390/molecules26216572

M3 - Article

C2 - 34770981

AN - SCOPUS:85120671229

SN - 1420-3049

VL - 26

JO - Molecules

JF - Molecules

IS - 21

M1 - 6572

ER -

Dibenzofuran derivatives inspired from cercosporamide as dual inhibitors of pim and CLK1 kinases

Abstract

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Cite this