Artículo
Lipase-Catalyzed Synthesis and Biological Evaluation of N-Picolineamides as Trypanosoma cruzi Antiproliferative Agents
Freije García, Fabricio Eloy
; Musikant, Alejandro Daniel
; Escalona Hernández, José Leonardo
; Edreira, Martin Miguel
; Linãres, Guadalupe Garciá
Fecha de publicación:
01/2023
Editorial:
American Chemical Society
Revista:
ACS Medicinal Chemistry Letters
ISSN:
1948-5875
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
In our search for new safe antiparasitic agents, an enzymatic pathway was applied to synthesize a series of N-pyridinylmethyl amides derived from structurally different carboxylic acids. Thirty derivatives, including 11 new compounds, were prepared through lipase-catalyzed acylation in excellent yields. In order to optimize the synthetic methodology, the impact of different reaction parameters was analyzed. Some compounds were evaluated as antiproliferative agents against Trypanosoma cruzi, the parasite responsible for American trypanosomiasis (Chagas' disease). Some of them showed significant activity as parasite proliferation inhibitors. Amides derived from 2-aminopicoline and stearic and elaidic acids were as potent as nifurtimox against the amastigote form of T. cruzi, the clinically relevant form of the parasite. Even more, a powerful synergism between nifurtimox and N-(pyridin-2-ylmethyl)stereamide was observed, almost completely inhibiting the proliferation of the parasite. Besides, the obtained compounds showed no toxicity in Vero cells, making them excellent potential candidates as lead drugs.
Palabras clave:
CHAGAS' DISEASE
,
ENZYMATIC SYNTHESIS
,
LIPASE
,
PICOLINE DERIVATIVES
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(IQUIBICEN)
Articulos de INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CS. EXACTAS Y NATURALES
Articulos de INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CS. EXACTAS Y NATURALES
Articulos(UMYMFOR)
Articulos de UNID.MICROANAL.Y MET.FISICOS EN QUIM.ORG.(I)
Articulos de UNID.MICROANAL.Y MET.FISICOS EN QUIM.ORG.(I)
Citación
Freije García, Fabricio Eloy; Musikant, Alejandro Daniel; Escalona Hernández, José Leonardo; Edreira, Martin Miguel; Linãres, Guadalupe Garciá; Lipase-Catalyzed Synthesis and Biological Evaluation of N-Picolineamides as Trypanosoma cruzi Antiproliferative Agents; American Chemical Society; ACS Medicinal Chemistry Letters; 14; 1; 1-2023; 59-65
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