Title:Flavonoid Derivatives Targeting BCR-ABL Kinase: Semisynthesis, Molecular Dynamic Simulations and Enzymatic Inhibition
Volume: 21
Issue: 22
Author(s): Rayssa Ribeiro, Mariana A. Eloy, Carla S. Francisco, Clara L. Javarini, Gabriela M. Ayusso, Victor Da Rocha Fonseca, Wanderson Romão, Luis O. Regasini, Sheila C. Araujo, Michell O. Almeida, Kathia M. Honorio, Heberth de Paula, Valdemar Lacerda *Pedro A. B. Morais
Affiliation:
- Programa de Pos-Graduacao em Quimica, Universidade Federal do Espirito Santo, 29075910, Vitoria- ES,Brazil
Keywords:
Semisynthesis, Triazole, BCR-ABL kinase inhibitors, Chronic myeloid leukemia, Williamson synthesis,
6-hydroxy-flavanone skeleton.
Abstract:
Background: Natural products have been universally approached in the research of novel
trends useful to detail the essential paths of the life sciences and as a strategy for pharmacotherapeutics.
Objective: This work focuses on further modification to the 6-hydroxy-flavanone building block
aiming to obtain improved BCR-ABL kinase inhibitors.
Methods: Ether derivatives were obtained from Williamson synthesis and triazole from Microwave-
assisted click reaction. Chemical structures were finely characterized through IR, 1H and
13C NMR and HRMS. They were tested for their inhibitory activity against BCR-ABL kinase.
Results: Two inhibitors bearing a triazole ring as a pharmacophoric bridge demonstrated the
strongest kinase inhibition at IC50 value of 364 nM (compound 3j) and 275 nM (compound 3k).
Conclusion: 6-hydroxy-flavanone skeleton can be considered as a promising core for BCR-ABL kinase
inhibitors.
