Peer-Reviewed Journal Details
Mandatory Fields
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
October
Molecules (Basel, Switzerland)
Dibenzofuran Derivatives Inspired from Cercosporamide as Dual Inhibitors of Pim and CLK1 Kinases.
Validated
()
Optional Fields
26
21
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.
1420-3049
10.3390/molecules26216572
Grant Details