Examinando por Autor "Camargo-Ayala, Lorena"

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    O-Alkyl derivatives of ferulic and syringic acid as lipophilic antioxidants: effect of the length of the alkyl chain on the improvement of the thermo-oxidative stability of sunflower oil
    (Royal Society of Chemistry, 2024-07-16) Forero-Doria, Oscar; Guzmán, Luis; Venturini, Whitney; Zapata-Gomez, Felipe; Duarte, Yorley; Camargo-Ayala, Lorena; Echeverría, Cesar; Echeverría, Javier
    Lipid oxidation is the major cause of the deterioration of fat-containing foods, especially those containing polyunsaturated fatty acids (PUFAs). Antioxidant additives of synthetic origin are added to matrices rich in PUFAs, such as sunflower oil (SO). However, there is controversy regarding their safety, and their low solubility in both water and fat has led to the search for new covalent modifications through lipophilicity. This work presents the synthesis of O-alkyl acid derivatives from ferulic and syringic acids and the study of their antioxidant capacity and effect on the thermoxidative degradation of SO. Antioxidant activities were evaluated by employing ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays in a concentration range of 10-100 µg mL−1. The IC50 values for DPPH scavenging activity ranged from 15.61-90.43 µg mL−1. The results of the FRAP assay for both O-alkyl ferulic (3a-f) and syringic (5a-f) series revealed a “cut-off” effect on antioxidant activity in carbon five (C5). Thermoxidation study of additives 3b-c and 5b-c showed a decrease in the slope of extinction coefficients K232 and K270 in comparison with SOcontrol. Furthermore, 3c presented higher antioxidant activity than 3b and 1, with a power to decrease the thiobarbituric acid reactive species (TBARS) 6 times higher than SOcontrol at 220 °C. Additives 5b-c exerted a protective effect on the thermoxidation of SO. The results suggest that increasing lipophilic and thermal properties of antioxidants through O-alkyl acid derivatization is an effective strategy for accessing lipophilic antioxidant additives with potential use in food matrices.
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    Rational design, synthesis, and evaluation of novel polypharmacological compounds targeting NaV1.5, KV1.5, and K2P channels for atrial fibrillation
    (American Society for Biochemistry and Molecular Biology Inc., 2025-04) Camargo-Ayala, Lorena; Bedoya, Mauricio; Dasí, Albert; Prüser, Merten; Schütte, Sven; Prent-Peñaloza, Luis; Adasme-Carreño, Francisco; Kiper, Aytug K.; Rinné, Susanne; Camargo-Ayala, Paola Andrea; Peña-Martínez, Paula A.; Bueno-Orovio, Alfonso
    Atrial fibrillation (AF) involves electrical remodeling of the atria, with ion channels such as NaV1.5, KV1.5, and TASK-1 playing crucial roles. This study investigates acetamide-based compounds designed as multi-target inhibitors of these ion channels to address AF. Compound 6f emerged as the most potent in the series, demonstrating a strong inhibition of TASK-1 (IC50 ∼ 0.3 μM), a moderate inhibition of NaV1.5 (IC50 ∼ 21.2 μM) and a subtle inhibition of KV1.5 (IC50 ∼ 81.5 μM), alongside unexpected activation of TASK-4 (∼ 40% at 100 μM). Functional assays on human atrial cardiomyocytes from sinus rhythm (SR) and patients with AF revealed that 6f reduced action potential amplitude in SR (indicating NaV1.5 block), while in AF it increased action potential duration (APD), reflecting high affinity for TASK-1. Additionally, 6f caused hyperpolarization of the resting membrane potential in AF cardiomyocytes, consistent with the observed TASK-4 activation. Mathematical modeling further validated its efficacy in reducing AF burden. Pharmacokinetic analyses suggest favorable absorption and low toxicity. These findings identify 6f as a promising multi-target therapeutic candidate for AF management.