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

Identification of a new series of flavopiridol-like structures as kinase inhibitors with high cytotoxic potency.
Eur J Med Chem. 2020 May 05;199:112355
Authors: Ibrahim N, Bonnet P, Brion JD, Peyrat JF, Bignon J, Levaique H, Josselin B, Robert T, Colas P, Bach S, Messaoudi S, Alami M, Hamze A
Abstract
In this work, unique 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 resulting from a structure-activity relationship (SAR) study and in silico docking showed the best antiproliferative activity and was more efficient than the reference compound. In addition, compound 13c showed significant nanomolar inhibition against CDK9, CDK10, and GSK3β protein kinases.
PMID: 32402934 [PubMed - as supplied by publisher]

Source: European Journal of Medicinal Chemistry - May 4, 2020 Category: Chemistry Authors: Ibrahim N, Bonnet P, Brion JD, Peyrat JF, Bignon J, Levaique H, Josselin B, Robert T, Colas P, Bach S, Messaoudi S, Alami M, Hamze A Tags: Eur J Med Chem Source Type: research