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Current Topics in Medicinal Chemistry


ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Research Article

Flavonoid Derivatives Targeting BCR-ABL Kinase: Semisynthesis, Molecular Dynamic Simulations and Enzymatic Inhibition

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 * and Pedro A. B. Morais

Volume 21, Issue 22, 2021

Published on: 05 July, 2021

Page: [1999 - 2017] Pages: 19

DOI: 10.2174/1568026621666210705170047

Price: $65


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.

Keywords: Semisynthesis, Triazole, BCR-ABL kinase inhibitors, Chronic myeloid leukemia, Williamson synthesis, 6-hydroxy-flavanone skeleton.

Graphical Abstract

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