Artículo
Azilsartan and its Zn(II) complex. Synthesis, anticancer mechanisms of action and binding to bovine serum albumin
Martinez, Valeria Romina
; Aguirre, María Victoria; Todaro, Juan Santiago; Piro, Oscar Enrique
; Echeverría, Gustavo Alberto
; Ferrer, Evelina Gloria
; Williams, Patricia Ana María
Fecha de publicación:
04/2018
Editorial:
Pergamon-Elsevier Science Ltd
Revista:
Toxicology in Vitro
ISSN:
0887-2333
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Azilsartan is the eighth approved member of angiotensin II receptor blockers for hypertension treatment. Considering that some drugs have additional effects when administered, we studied its effects and mechanisms of action on ahuman lung cancer cell line A549. We have also modified the structure of the drug by complexation with Zn(II) cation and assayed the anticancer effect. The crystal structure of the new binuclear Zn(II) complex, for short[Zn2(azil)2(H2O)4]·2H2O (ZnAzil), was determined by X-ray diffraction methods. The zinc ions are bridged by azilsartan ligands through their carboxylate oxygen and oxadiazol nitrogen atoms. The compounds were examined for their cytotoxic effects against human lung fibroblast (MRC5) and human lung cancer (A549) cell lines. Azilsartan displayed low cytotoxic effects at 150 μM concentrations in A549 human lung cancer cells but the higher effect measured for the Zn complex suggested that this compound may act as an anticancer agent. An apoptotic oxidative stress mechanism of action via the mitochondrial-dependent intrinsic pathway has been determined. Besides, the compounds exerted weak cytotoxic effects in the normal lung related cell line MRC5. Binding constants of the complex formed between each compound and bovine serum albumin (BSA) are in the intermediate range, hence suggesting that azilsartan and ZnAzil could be bonded and transported by BSA
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Articulos(CEQUINOR)
Articulos de CENTRO DE QUIMICA INORGANICA "DR. PEDRO J. AYMONINO"
Articulos de CENTRO DE QUIMICA INORGANICA "DR. PEDRO J. AYMONINO"
Articulos(IFLP)
Articulos de INST.DE FISICA LA PLATA
Articulos de INST.DE FISICA LA PLATA
Citación
Martinez, Valeria Romina; Aguirre, María Victoria; Todaro, Juan Santiago; Piro, Oscar Enrique; Echeverría, Gustavo Alberto; et al.; Azilsartan and its Zn(II) complex. Synthesis, anticancer mechanisms of action and binding to bovine serum albumin; Pergamon-Elsevier Science Ltd; Toxicology in Vitro; 48; 4-2018; 205-220
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