Improvement of the antihypertensive capacity of candesartan and trityl candesartan by their SOD mimetic copper(II) complexes

Islas, María Soledad; Rojo, Teófilo; Lezama, Luís; Merino, Mercedes Griera; Cortés, María Alicia; Puyol, Manuel Rodríguez; Ferrer, Evelina G.; Williams, Patricia Ana María

doi:10.1016/j.jinorgbio.2013.02.005

Cited by 13 publications

(4 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The statistical analysis of the data shows no difference between them, with an inhibition close to 40 % at the maximum concentration tested (100 μM). For CuAlk, the measured SOD activity (IC 50 = 0.69 μM) (Table 2) is significantly lower than the corresponding value obtained for the metallic cation and comparable to the activity reported for the bovine enzyme (IC 50 =0.21 μM) [26]. Alk base has not shown significant activity since at the maximum concentration tested (100 μM), an inhibition of only the 65 % of the NBT reduction was observed.…”

Section: Antioxidant Activitiessupporting

confidence: 56%

See 1 more Smart Citation

Aliskiren Copper(II) Complex. Synthesis and Antioxidant Activity

Jori,

Islas,

Ferrer

et al. 2024

J. Mex. Chem. Soc.

View full text Add to dashboard Cite

Abstract. Aliskiren (Alk) is a highly selective competitive inhibitor of renin used for the treatment of hypertension and related cardiovascular diseases. With the aim of improving its biological properties by the strategy of the induction of favorable conformational changes, we designed a metal-based drug. In this work we report the synthesis of a solid copper(II) complex with aliskiren, CuAlk, and its characterization in solution and solid-state. Moreover, and based on the association of hypertension with elevated levels of reactive oxygen species (ROS), the antioxidant properties of CuAlk were studied measuring the activities against 2,2-diphenyl-1-picrilhidrazil (DPPH·), hydroxyl (OH·) and peroxyl (ROO·) radicals, in addition to its superoxide dismutase (SOD) simil activity. Both the ligand and the complex were able to scavenge hydroxyl radicals, but upon complexation, the SOD mimetic activity of the ligand is enhanced. Resumen. El Aliskiren (Alk) es un inhibidor por competencia altamente selectivo de la renina que se utiliza en el tratamiento de la hipertensión y enfermedades cardiovasculares relacionadas. Se diseñó un metalofármaco con la idea de mejorar las propiedades biológicas mediante la inducción de cambios conformacionales favorables. En este trabajo se reporta la síntesis de un complejo sólido de cobre(II) con aliskiren, CuAlk, junto con su caracterización en fase sólida y en solución. Además, de acuerdo con la relación que existe entre la hipertensión y los niveles elevados de especies reactivas de oxígeno (ROS), se estudian las propiedades antioxidantes del CuAlk frente a los radicales 2,2-difenil-1-picrilhidracilo (DPPH·), hidroxilo (OH·) y peroxilo (ROO·), además de la actividad superóxido dismutasa símil (SOD). Tanto el ligando, como el complejo fueron capaces de secuestrar radicales hidroxilos, pero, luego de la complejación, se mejoró la actividad SOD símil del ligando.

show abstract

Section: Antioxidant Activitiessupporting

confidence: 56%

“…The antioxidant properties of the free ligand and CuAlk were studied by different techniques: the scavenging power of the DPPH • , the scavenging of OH • radical, the inhibition of the production of peroxyl radical (ROO • , lag phase) and the ability of mimic the SOD activity according to previously reported methods [26].…”

Section: Antioxidant Activitiesmentioning

confidence: 99%

Aliskiren Copper(II) Complex. Synthesis and Antioxidant Activity

Jori,

Islas,

Ferrer

et al. 2024

J. Mex. Chem. Soc.

View full text Add to dashboard Cite

show abstract

“…The antioxidant assays (superoxide dismutase (SOD) activity, antiradical 1,1-diphenyl-2-picrylhydrazyl radical (DPPH Å ), 2,2 0azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt decoloration assay, scavenging of the hydroxyl radical and the inhibition of peroxyl radical) were performed according to our previously reported techniques [15]. In these experiments morin and VOmor complex were dissolved in the minimum quantity of DMSO and they were added to the aqueous buffer and the substrate solutions.…”

Section: Antioxidant Propertiesmentioning

confidence: 99%

Biological evaluation of morin and its new oxovanadium(IV) complex as antio-xidant and specific anti-cancer agents

Naso

Lezama

Rojo

et al. 2013

Chemico-Biological Interactions

Self Cite

View full text Add to dashboard Cite

“…However, Losartan has been described to spontaneously form an insoluble complex with Cu 81, and ARB-Cu complexes have been reported to display anti-oxidant activity 828384, pointing to the possibility of Cu-chelation by ARBs. Whether the underlying mechanistic event that governs the ARB-mediated protection against Cu-induced toxicity is attributed to Cu complexation by ARBs has yet to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II type 1 receptor blockers increase tolerance of cells to copper and cisplatin

Spincemaille

Chandhok

Zibert

et al. 2014

MIC

View full text Add to dashboard Cite

The human pathology Wilson disease (WD) is characterized by toxic copper (Cu) accumulation in brain and liver, resulting in, among other indications, mitochondrial dysfunction and apoptosis of hepatocytes. In an effort to identify novel compounds that can alleviate Cu-induced toxicity, we screened the Pharmakon 1600 repositioning library using a Cu-toxicity yeast screen. We identified 2 members of the drug class of Angiotensin II Type 1 receptor blockers (ARBs) that could increase yeast tolerance to Cu, namely Candesartan and Losartan. Subsequently, we show that specific ARBs can increase yeast tolerance to Cu and/or the chemotherapeutic agent cisplatin (Cp). The latter also induces mitochondrial dysfunction and apoptosis in mammalian cells. We further demonstrate that specific ARBs can prevent the prevalence of Cu-induced apoptotic markers in yeast, with Candesartan Cilexetil being the ARB which demonstrated most pronounced reduction of apoptosis-related markers. Next, we tested the sensitivity of a selection of yeast knockout mutants affected in detoxification of reactive oxygen species (ROS) and Cu for Candesartan Cilexetil rescue in presence of Cu. These data indicate that Candesartan Cilexetil increases yeast tolerance to Cu irrespectively of major ROS-detoxifying proteins. Finally, we show that specific ARBs can increase mammalian cell tolerance to Cu, as well as decrease the prevalence of Cu-induced apoptotic markers. All the above point to the potential of ARBs in preventing Cu-induced toxicity in yeast and mammalian cells.

show abstract

Improvement of the antihypertensive capacity of candesartan and trityl candesartan by their SOD mimetic copper(II) complexes

Cited by 13 publications

References 46 publications

Aliskiren Copper(II) Complex. Synthesis and Antioxidant Activity

Aliskiren Copper(II) Complex. Synthesis and Antioxidant Activity

Biological evaluation of morin and its new oxovanadium(IV) complex as antio-xidant and specific anti-cancer agents

Angiotensin II type 1 receptor blockers increase tolerance of cells to copper and cisplatin

Contact Info

Product

Resources

About