European Journal of Pharmaceutical Sciences (2019)
Update date:2022-08-30
Topics:
Guimar?es, Daniel Silqueira Martins
de Sousa Luz, Letícia Silveira
do Nascimento, Sara Batista
Silva, Lorena Rabelo
de Miranda Martins, Natália Rezende
de Almeida, Heloísa Gon?alves
de Souza Reis, Vitória
Maluf, Sarah El Chamy
Budu, Alexandre
Marinho, Juliane Aparecida
Abramo, Clarice
Carmona, Adriana Karaoglanovic
da Silva, Marina Goulart
da Silva, Gisele Rodrigues
Kemmer, Victor Matheus
Butera, Anna Paola
Ribeiro-Viana, Renato Márcio
Gazarini, Marcos Leoni
Júnior, Clébio Soares Nascimento
Guimar?es, Luciana
dos Santos, Fabio Vieira
de Castro, Whocely Victor
Viana, Gustavo Henrique Ribeiro
de Brito, Cristiana Ferreira Alves
de Pilla Varotti, Fernando
The development of new antimalarial drugs is urgent to overcome the spread of resistance to the current treatment. Herein we synthesized the compound 3, a hit-to?lead optimization of a thiazole based on the most promising 3-alkylpyridine marine alkaloid analog. Compound 3 was tested against Plasmodium falciparum and has shown to be more potent than its precursor (IC50 values of 1.55 and 14.7 μM, respectively), with higher selectivity index (74.7) for noncancerous human cell line. This compound was not mutagenic and showed genotoxicity only at concentrations four-fold higher than its IC50. Compound 3 was tested in vivo against Plasmodium berghei NK65 strain and inhibited the development of parasite at 50 mg/kg. In silico and UV–vis approaches determined that compound 3 acts impairing hemozoin crystallization and confocal microscopy experiments corroborate these findings as the compound was capable of diminishing food vacuole acidity. The assay of uptake using human intestinal Caco-2 cell line showed that compound 3 is absorbed similarly to chloroquine, a standard antimalarial agent. Therefore, we present here compound 3 as a potent new lead antimalarial compound.
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Doi:10.1007/BF00568017
()Doi:10.1016/j.apcata.2017.06.010
(2017)Doi:10.1016/S0040-4039(00)94278-3
(1983)Doi:10.1007/BF02698792
(1978)Doi:10.1021/jo00297a036
(1990)Doi:10.1007/BF00757848
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