lavonoid Derivatives Targeting BCR-ABL Kinase: Semisynthesis, Molecular Dynamic Simulations and Enzymatic Inhibitio

Autor(es):Mostrar menos -

Ribeiro, Rayssa ^[1] ; Eloy, Mariana A. ^[1] ; Francisco, Carla S. ^[2] ; Javarini, Clara L. ^[2] ; Ayusso, Gabriela M. ^[3] ; Fonseca, Victor Da Rocha ^[2] ; Romao, Wanderson ^[2] ; Regasini, Luis O. ^[3] ; Araujo, Sheila C. ^[4] ; Almeida, Michell O. ^[5] ; Honorio, Kathia M. ^{[6, 4]} ; de Paula, Heberth ^[7] ; Lacerda Jr, Valdemar ; Morais, Pedro A. B. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Espirito Santo, Programa Posgrad Agroquim, BR-29500000 Alegre, ES - Brazil

^[2] Univ Fed Espirito Santo, Programa Posgrad Quim, BR-29075910 Vitoria, ES - Brazil

^[3] Univ Estadual Paulista, Programa Posgrad Microbiol, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil

^[4] Fed Univ ABC, CCNH, BR-09210580 Santo Andre, SP - Brazil

^[5] Inst Quim Sao Carlos USP, BR-13563120 Sao Carlos, SP - Brazil

^[6] Univ Sao Paulo, Escola Artes Ciencias & Humanidades, BR-03828000 Sao Paulo, SP - Brazil

^[7] Univ Fed Espirito Santo, Ctr Ciencias Exatas Nat & Saude, BR-29500000 Alegre, ES - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CURRENT TOPICS IN MEDICINAL CHEMISTRY; v. 21, n. 22, p. 1999-2017, 2021.
• Citações Web of Science: 2

Resumo

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, H-1 and C-13 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. (AU)

• Processo FAPESP: 17/10118-0 - Estudo e aplicação da tecnologia eletroquímica para a análise e a degradação de interferentes endócrinos: materiais, sensores, processos e divulgação científica
• Beneficiário: Marcos Roberto de Vasconcelos Lanza
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/24524-7 - Análise estrutural e estudos de modelagem molecular para ligantes de origem natural e sintética relacionados a doenças negligenciadas
• Beneficiário: Kathia Maria Honorio
• Modalidade de apoio: Auxílio à Pesquisa - Regular