Identification of a new series of flavopiridol-like structures as kinase inhibitors with high cytotoxic potency

Autor: Mouad Alami, Jean-Daniel Brion, Pascal Bonnet, Abdallah Hamze, Nada Ibrahim, Pierre Colas, Jean-François Peyrat, Thomas Robert, Samir Messaoudi, Jérôme Bignon, Stéphane Bach, Béatrice Josselin, Hélène Levaique
Přispěvatelé: Biomolécules : Conception, Isolement, Synthèse (BioCIS), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-CY Cergy Paris Université (CY), Institut de Chimie Organique et Analytique (ICOA), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Fédération de recherche de Roscoff (FR2424), Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Messaoudi, Samir
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Stereochemistry
[CHIM.THER] Chemical Sciences/Medicinal Chemistry
Antineoplastic Agents
[CHIM.THER]Chemical Sciences/Medicinal Chemistry
Favopiridol
01 natural sciences
Thiosugars
03 medical and health sciences
chemistry.chemical_compound
Structure-Activity Relationship
Thioether
Piperidines
Drug Discovery
Tumor Cells
Cultured
Structure–activity relationship
Cytotoxic T cell
Humans
Cytotoxicity
Kinase inhibition
Protein Kinase Inhibitors
030304 developmental biology
Cell Proliferation
Pharmacology
chemistry.chemical_classification
Flavonoids
0303 health sciences
Dose-Response Relationship
Drug
Molecular Structure
010405 organic chemistry
Kinase
Organic Chemistry
[CHIM.CATA] Chemical Sciences/Catalysis
General Medicine
[CHIM.CATA]Chemical Sciences/Catalysis
In vitro
structure-activity relationship. Highlights
0104 chemical sciences
3. Good health
Amino acid
Molecular Docking Simulation
chemistry
cytotoxicity
Drug Screening Assays
Antitumor
Protein Kinases
Zdroj: European Journal of Medicinal Chemistry
European Journal of Medicinal Chemistry, Elsevier, 2020, 199 (31), pp.112355. ⟨10.1016/j.ejmech.2020.112355⟩
European Journal of Medicinal Chemistry, 2020, 199 (31), pp.112355. ⟨10.1016/j.ejmech.2020.112355⟩
ISSN: 0223-5234
1768-3254
Popis: International audience; In this work, unique structure of flavopiridol analogs bearing thiosugars, amino acids and heterocyclic moieties tethered to the flavopiridol via thioether and amine bonds mainly on its C ring have been prepared. The analogs bearing thioether-benzimidazoles as substituents have demonstrated high cytotoxic activity in vitro against up to seven cancer cell lines. Their cytotoxic effects are comparable to those of flavopiridol. The most active compound (13c) found after the structure-activity relationship (SAR) showed the best antiproliferative activity and was more efficient than the reference compound. In addition, compound 13c showed significant nanomolar inhibition against CDK9 and GSK3β protein kinases.
Databáze: OpenAIRE
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