Synthesis and biological evaluation of selected 7H-pyrrolo[2,3-d]pyrimidine derivatives as novel CDK9/CyclinT and Haspin inhibitors.


Journal

Chemico-biological interactions
ISSN: 1872-7786
Titre abrégé: Chem Biol Interact
Pays: Ireland
ID NLM: 0227276

Informations de publication

Date de publication:
01 Nov 2021
Historique:
received: 30 05 2021
revised: 07 08 2021
accepted: 06 09 2021
pubmed: 12 9 2021
medline: 9 11 2021
entrez: 11 9 2021
Statut: ppublish

Résumé

Protein kinases, including CDK9/CyclinT and Haspin, are regarded as potential drug targets in cancer therapy. Findings from a previous study suggested 7-azaindole as a privileged scaffold for producing inhibitors of CDK9/CyclinT and Haspin. Inspired by these findings, the current study synthesised and evaluated thirteen (13) C6-substituted 7-azaindole and twenty (20) C4-substituted structurally related 7H-pyrrolo[2,3-d]pyrimidine derivatives against a panel of protein kinases, including CDK9/CyclinT and Haspin. Eleven of the 7H-pyrrolo[2,3-d]pyrimidine derivatives exhibited activity toward CDK9/CyclinT, while 4 of compounds had activity against Haspin. The best CDK9/CyclinT (IC

Identifiants

pubmed: 34508710
pii: S0009-2797(21)00281-7
doi: 10.1016/j.cbi.2021.109643
pii:
doi:

Substances chimiques

Antineoplastic Agents 0
Cyclin T 0
Intracellular Signaling Peptides and Proteins 0
Pyrimidines 0
HASPIN protein, human EC 2.7.11.1
Protein Serine-Threonine Kinases EC 2.7.11.1
CDK9 protein, human EC 2.7.11.22
Cyclin-Dependent Kinase 9 EC 2.7.11.22
pyrimidine K8CXK5Q32L

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

109643

Informations de copyright

Copyright © 2021 Elsevier B.V. All rights reserved.

Auteurs

Lianie Pieterse (L)

Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa.

Richard M Beteck (RM)

Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa.

Blandine Baratte (B)

Sorbonne Université, CNRS, UMR8227, Integrative Biology of Marine Models Laboratory (LBI2M), Station Biologique de Roscoff, 29680, Roscoff, France; Sorbonne Université, CNRS, FR2424, Plateforme de Criblage KISSf (Kinase Inhibitor Specialized Screening Facility), Station Biologique de Roscoff, 29680, Roscoff Cedex, France.

Omobolanle J Jesumoroti (OJ)

Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa.

Thomas Robert (T)

Sorbonne Université, CNRS, UMR8227, Integrative Biology of Marine Models Laboratory (LBI2M), Station Biologique de Roscoff, 29680, Roscoff, France; Sorbonne Université, CNRS, FR2424, Plateforme de Criblage KISSf (Kinase Inhibitor Specialized Screening Facility), Station Biologique de Roscoff, 29680, Roscoff Cedex, France.

Sandrine Ruchaud (S)

Sorbonne Université, CNRS, UMR8227, Integrative Biology of Marine Models Laboratory (LBI2M), Station Biologique de Roscoff, 29680, Roscoff, France.

Stéphane Bach (S)

Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa; Sorbonne Université, CNRS, UMR8227, Integrative Biology of Marine Models Laboratory (LBI2M), Station Biologique de Roscoff, 29680, Roscoff, France; Sorbonne Université, CNRS, FR2424, Plateforme de Criblage KISSf (Kinase Inhibitor Specialized Screening Facility), Station Biologique de Roscoff, 29680, Roscoff Cedex, France.

Lesetja J Legoabe (LJ)

Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa. Electronic address: Lesetja.Legoabe@nwu.ac.za.

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Classifications MeSH