CEQUINOR   05415
CENTRO DE QUIMICA INORGANICA "DR. PEDRO J. AYMONINO"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Antitumor (in vitro) and antihypertensive (in vivo) effects of a new coordination complex formed with the drug telmisartan and the biometal Zn(II).
Autor/es:
MARTÍNEZ, VALERIA R.; FERRER, EVELINA; AGUIRRE, MARÍA V.; WILLIAMS, PATRICIA A.M.; TODARO, JUAN S.
Lugar:
Birmingham
Reunión:
Conferencia; EuroBIC14; 2018
Institución organizadora:
SBIC
Resumen:
Considering thatthe biological activities of some drugs can be improved by their structuralmodification, the structure of the antihypertensive agent telmisartan (Tlm) wasmodified through its interaction with the biometal Zn. The obtained complex [Zn(Tlm)2].4H2O(ZnTlm) was characterized by elemental analysis, thermogravimetricdeterminations and spectroscopic techniques (FTIR, NMR). The antitumor activitywas measured in the human lung cancer cell line A549 and the probablemechanisms of action were determined. The complex markedly improved thedeleterious effect on the tumor line, with a value of IC50 of 75 μM(IC50 125 μM for telmisartan, IC50 225 μM for ZnSO4).The cellular oxidative stress generation for ZnTlm (increase in reactive oxygenspecies and decrease in cellular reducing species (glutathione/oxidizedglutathione, GSH/GSSG)) induced an apoptotic mechanism: increase in the BAX/Bcl-XL((pro-apoptotic protein)/(antiapoptotic protein)) ratio and caspase-3activation. The complex generated 47.5% of apoptotic cells (TUNEL) and telmisartaninduced 39% of necrosis (staining with acridine orange and ethidium bromide).Both the complex and the ligand bind to bovine serum albumin (BSA), theinteraction of the complex being greater. The calculated binding constants werein the order of 105 M-1 and an electrostatic interactionmechanism was determined. Moreover, the ZnTlm complex produced a slightlyhigher blood pressure reduction than the antihypertensive drug telmisartanafter 6 days of treatment. This effect was measured in a hypertensive rat modelby chronic administration of L-NAME (N-Nitro-L-arginine methyl ester hydrochloride).Theadministration of ZnSO4 did not modify the values ​​of the positivecontrol. The complex counteracted the morphological modifications of the aorticartery rings (reducing aortic hypertrophy) produced by L-NAME to a greaterextent than Telmisartan. The Zn(II) ion produced no effect. Therefore, it canbe shown that the coordination of the drug with the Zn(II) ion produces animprovement in the antitumor activity, a better interaction with BSA and anantihypertensive effect somehow greater in comparison with the commercial drug.