Guimaraes, Daniel Silqueira Martins; Luz, Leticia Silveira de Sousa; Batista do Nascimento, Sara; Silva, Lorena Rabelo; Martins, Natalia Rezende de Miranda; Goncalves de Almeida, Heloisa; Reis, Vitoria de Souza; Maluf, Sarah El Chamy; Budu, Alexandre; Marinho, Juliane Aparecida; Abramo, Clarice; Carmona, Adriana Karaoglanovic; Goulart da Silva, Marina; Rodrigues da Silva, Gisele; Kemmer, Victor Matheus; Butera, Anna Paola; Ribeiro-Viana, Renato Marcio; Gazarini, Marcos Leoni; Nascimento, Clebio Soares Jr.; Guimaraes, Luciana; Vieira dos Santos, Fabio; Victor de Castro, Whocely; Viana, Gustavo Henrique Ribeiro; Alves de Brito, Cristiana Ferreira; Varotti, Fernando de Pilla published the artcile< Improvement of antimalarial activity of a 3-alkylpiridine alkaloid analog by replacing the pyridine ring to a thiazole-containing heterocycle: Mode of action, mutagenicity profile, and Caco-2 cell-based permeability>, Application In Synthesis of 96-53-7, the main research area is colorectal adenocarcinoma cell permeability mutagenicity alkylpiridine alkaloid analog antimalarial; 3-Alkylpyridine marine alkaloid analogs; Antiplasmodial activity; Ferriprotoporphyrin-IX; Malaria; Plasmodium falciparum; Thiazole.
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 14.7μM, resp.), 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
European Journal of Pharmaceutical Sciences published new progress about Antimalarials. 96-53-7 belongs to class thiazole, and the molecular formula is C3H5NS2, Application In Synthesis of 96-53-7.
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica