Author(s):
Ribeiro, Rayssa ; Eloy, Mariana A. ; Francisco, Carla S. ; Javarini, Clara L. ; Ayusso, Gabriela M. [UNESP] ; Fonseca, Victor Da Rocha ; Romão, Wanderson ; Regasini, Luis O. [UNESP] ; Araujo, Sheila C. ; Almeida, Michell O. ; Honorio, Kathia M. ; Paula, Heberth de ; Lacerda, Valdemar ; Morais, Pedro A. B.
Date: 2022
Persistent ID: http://hdl.handle.net/11449/223132
Origin: Oasisbr
Subject(s): 6-hydroxy-flavanone skeleton; BCR-ABL kinase inhibitors; Chronic myeloid leukemia; Semisynthesis; Triazole; Williamson synthesis
Description
Made available in DSpace on 2022-04-28T19:48:50Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-09-01
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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 pharmacothera-peutics. 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 Mi-crowave-assisted click reaction. Chemical structures were finely characterized through IR,1H and13 C 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.
Programa de Pós-Graduação em Agroquímica Universidade Federal do Espírito Santo, ES
Programa de Pós-Graduação em Química Universidade Federal do Espírito Santo, ES
Programa de Pós-Graduação em Microbiologia Universidade Estadual Paulista Julio de Mesquita Fil-ho, SP
CCNH Federal University of ABC, SP
Instituto de Química de São Carlos-USP, SP
Escola de Artes Ciên-cias e Humanidades University of São Paulo, SP
Centro de Ciências Exatas Naturais e da Saúde Universidade Federal do Espírito Santo, ES
Programa de Pós-Graduação em Microbiologia Universidade Estadual Paulista Julio de Mesquita Fil-ho, SP
CAPES: 001
