Authors: Facchinetti, V. ; Gomes, C.R.B.; Aboud, K.; Fiorot, R.; De Carvalho, G.; Paier, C.R.; Do Ó Pessoa, C.; Gomes, A.C. ; De Souza, M.V.N.; Vasconcelos, T.R.A.
Source: Journal of the Brazilian Chemical Society, v. 35(2), p. e-20230139, 2024
Publisher: Brazilian Chemical Society
Abstract
This work describes the multigram-scale synthesis of the building-block N1-(7-chloroquinolin-4-yl)ethane-1,2-diamine via sonochemistry and its use in the synthesis of seven new quinoline-thiazole hybrids endowed with interesting anticancer activity. Target compounds were planned based on the drugs chloroquine and primaquine and the desired thiazoles were obtained through the Hantzsch thiazole synthesis, without the use of catalysts, by reacting key
intermediate 1-(2-((7-chloroquinolin-4-yl)amino)ethyl)thiourea, obtained in two-steps from N1-(7-chloroquinolin-4-yl)ethane-1,2-diamine, with different 2-bromoacetophenones. The novel molecules were assessed against four different leukemia cell lines (HL60, K562, KASUMI-1, and KG-1) plus normal fibroblasts (L929), using the 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-
2H-tetrazolium bromide (MTT) assay, and showed, overall, a high cytotoxic profile, but with interesting selectivity index, especially against K562 cells (1.89 to 5.50), when compared to standard doxorubicin (3.51). Docking studies suggest that all tested derivatives are able to interact with BCR-ABL1 tyrosine kinase enzyme, and, therefore, these molecules may be promising leads
against chronic myeloid leukemia.
Document Type: Research Article
DOI: 10.21577/0103-5053.20230139
Publication date: 17 de agosto de 2023
