2. Academic Validation
  3. Synthesis and evaluation of 7-azaindole derivatives bearing benzocycloalkanone motifs as protein kinase inhibitors

Synthesis and evaluation of 7-azaindole derivatives bearing benzocycloalkanone motifs as protein kinase inhibitors

  • Bioorg Med Chem. 2020 Jun 1;28(11):115468. doi: 10.1016/j.bmc.2020.115468.
Malikotsi A Qhobosheane 1,  Lesetja J Legoabe 2,  Béatrice Josselin 3,  Stéphane Bach 3,  Sandrine Ruchaud 4,  Jacobus P Petzer 5,  Richard M Beteck 1
Affiliations

Affiliations

  • 1 Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa.
  • 2 Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa. Electronic address: lesetja.legoabe@nwu.ac.za.
  • 3 Sorbonne Université, CNRS, UMR 8227, Integrative Biology of Marine Models Laboratory (LBI2M), Station Biologique de Roscoff, 29680 Roscoff, France; Sorbonne Université, CNRS, FR 2424, Plateforme de criblage KISSf (Kinase Inhibitor Specialized Screening facility), Station Biologique de Roscoff, 29680 Roscoff, France.
  • 4 Sorbonne Université, CNRS, UMR 8227, Integrative Biology of Marine Models Laboratory (LBI2M), Station Biologique de Roscoff, 29680 Roscoff, France.
  • 5 Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa; Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa.
PMID: 32284225 DOI: 10.1016/j.bmc.2020.115468
Abstract

Protein kinases are important drug targets, especially in the area of oncology. This paper reports the synthesis and biological evaluation of new 7-azaindole derivatives bearing benzocycloalkanone motifs as potential protein kinase inhibitors. Four compounds 8g, 8h, 8i, and 8l were discovered to inhibit cyclin-dependent kinase 9 (CDK9/CyclinT) and/or Haspin Kinase in the micromolar to nanomolar range. 8l was identified as the most potent Haspin inhibitor (IC50 = 14 nM), while 8g and 8h acted as dual inhibitors of CDK9/CyclinT and Haspin. These novel compounds constitute a promising starting point for the discovery of dual protein kinase inhibitors that have potential to be developed as Anticancer agents, since both CDK9/CyclinT and Haspin are considered to be drug targets in oncology.

Keywords

7-azaindole; Benzocycloalkanone; CDK9/CyclinT; Dual inhibitor; Haspin; Oncology; Protein kinase; Structure-activity relationship.

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