2. Academic Validation
  3. Synthesis of new pyrazolo[4,3-a]phenanthridine Pim-1 inhibitors and evaluation of their cytotoxic activity towards the MOLM-13 acute myeloid leukemia cell line

Synthesis of new pyrazolo[4,3-a]phenanthridine Pim-1 inhibitors and evaluation of their cytotoxic activity towards the MOLM-13 acute myeloid leukemia cell line

  • Bioorg Med Chem Lett. 2022 Oct 1:73:128914. doi: 10.1016/j.bmcl.2022.128914.
Etienne Auvert 1,  Reidun Aesoy 2,  Francis Giraud 1,  Lars Herfindal 2,  Fabrice Anizon 3,  Pascale Moreau 4
Affiliations

Affiliations

  • 1 Université Clermont Auvergne, CNRS, Clermont Auvergne INP, ICCF, F-63000 Clermont-Ferrand, France.
  • 2 Centre for Pharmacy, Department of Clinical Science, University of Bergen, Bergen, Norway.
  • 3 Université Clermont Auvergne, CNRS, Clermont Auvergne INP, ICCF, F-63000 Clermont-Ferrand, France. Electronic address: fabrice.anizon@uca.fr.
  • 4 Université Clermont Auvergne, CNRS, Clermont Auvergne INP, ICCF, F-63000 Clermont-Ferrand, France. Electronic address: pascale.moreau@uca.fr.
PMID: 35917834 DOI: 10.1016/j.bmcl.2022.128914
Abstract

We synthesized new analogues of the anti-AML agent VS-II-173. We studied the effect of the substitution at the 1- and 5-positions of the pyrazolo[4,3-a]phenanthridine scaffold on Pim-1 kinase inhibition and cytotoxicity against AML MOLM-13 cells. We found that compounds 20 and 21, substituted at the 1-position exhibited stronger Pim-1 inhibition together with a high potency toward MOLM-13 cells, associated with Apoptosis induction and selectivity over non-cancerous NRK cells.

Keywords

Acute myeloid leukemia; Antiproliferative activity; Pim kinase inhibitors; Pyrazolo[4,3-a]phenanthridine.

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