Browsing by Author "Pozo-Martinez, Josue"

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    Assessment of the Activity of Nitroisoxazole Derivatives against Trypanosoma cruzi
    (2024) Moncada-Basualto, Mauricio; Saavedra-Olavarria, Jorge; Rivero-Jerez, Paula S.; Rojas, Cristian; Maya, Juan D.; Liempi, Ana; Zuniga-Bustos, Matias; Olea-Azar, Claudio; Lapier, Michel; Perez, Edwin G.; Pozo-Martinez, Josue
    The development of new compounds to treat Chagas disease is imperative due to the adverse effects of current drugs and their low efficacy in the chronic phase. This study aims to investigate nitroisoxazole derivatives that produce oxidative stress while modifying the compounds' lipophilicity, affecting their ability to fight trypanosomes. The results indicate that these compounds are more effective against the epimastigote form of T. cruzi, with a 52 +/- 4% trypanocidal effect for compound 9. However, they are less effective against the trypomastigote form, with a 15 +/- 3% trypanocidal effect. Additionally, compound 11 interacts with a higher number of amino acid residues within the active site of the enzyme cruzipain. Furthermore, it was also found that the presence of a nitro group allows for the generation of free radicals; likewise, the large size of the compound enables increased interaction with aminoacidic residues in the active site of cruzipain, contributing to trypanocidal activity. This activity depends on the size and lipophilicity of the compounds. The study recommends exploring new compounds based on the nitroisoxazole skeleton, with larger substituents and lipophilicity to enhance their trypanocidal activity.
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    Polyphenolic Composition and Antioxidant Activity (ORAC, EPR and Cellular) of Different Extracts of Argylia radiata Vitroplants and Natural Roots
    (2022) Giordano, Ady; Morales-Tapia, Pablo; Moncada-Basualto, Mauricio; Pozo-Martinez, Josue; Olea-Azar, Claudio; Nesic, Aleksandra; Cabrera-Barjas, Gustavo
    Plant biochemistry studies have increased in recent years due to their potential to improve human health. Argylia radiata is an extremophile plant with an interesting polyphenolic profile. However, its biomass is scarce and occasionally available. Argylia in vitro biomass was obtained from tissue culture and compared with in vivo roots regarding its polyphenolic and flavonoid content. Different solvents were used to prepare extracts from the in vitro tissue of callus and aerial plant organs and in vivo roots. UPLC-MS/MS was used to assess the chemical composition of each extract. ORAC-FL and scavenging of free radicals (DPPH and OH) methods were used to determine the antioxidant capacity of extracts. Furthermore, the biological activity of the extracts was established using the cellular antioxidant activity method. The vitroplants were a good source of polyphenols (25-68 mg GAE/100 g tissue FW), and methanol was the most efficient solvent. Eight polyphenolic compounds were identified, and their antioxidant properties were investigated by different chemical methods with EPR demonstrating its specific scavenging activity against free radicals. All extracts showed cellular dose-dependent antioxidant activity. The methanolic extract of vitroplants showed the highest cellular antioxidant activity (44.6% and 51%) at 1 and 10 mu g/mL of extract, respectively. Vitroplants of A. radiata are proposed as a biotechnological product as a source of antioxidant compounds with multiple applications.
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    Safety and Pharmacokinetics of a Combined Antioxidant Therapy against Myocardial Reperfusion Injury: A Phase I Randomized Clinical Trial in Healthy Humans
    (2024) Gajardo Cortez, Abraham I. J.; Lillo-Moya, Jose; San-Martin-Martinez, Daniel; Pozo-Martinez, Josue; Morales, Pablo; Prieto, Juan C.; Aguayo, Ruben; Puentes, Angel; Ramos, Cristobal; Silva, Solange; Catalan, Mabel; Ramos, Karla; Olea-Azar, Claudio; Rodrigo, Ramon
    Myocardial reperfusion injury (MRI) accounts for up to 50% of the final size in acute myocardial infarction and other conditions associated with ischemia-reperfusion. Currently, there is still no therapy to prevent MRI, but it is well known that oxidative stress has a key role in its mechanism. We previously reduced MRI in rats through a combined antioxidant therapy (CAT) of ascorbic acid, N-acetylcysteine, and deferoxamine. This study determines the safety and pharmacokinetics of CAT in a Phase I clinical trial. Healthy subjects (n = 18) were randomized 2:1 to CAT or placebo (NaCl 0.9% i.v.). Two different doses/infusion rates of CATs were tested in a single 90-minute intravenous infusion. Blood samples were collected at specific times for 180 minutes to measure plasma drug concentrations (ascorbic acid, N-acetylcysteine, and deferoxamine) and oxidative stress biomarkers. Adverse events were registered during infusion and followed for 30 days. Both CAT1 and CAT2 significantly increased the CAT drug concentrations compared to placebo (P < .05). Most of the pharmacokinetic parameters were similar between CAT1 and CAT2. In total, 6 adverse events were reported, all nonserious and observed in CAT1. The ferric-reducing ability of plasma (an antioxidant biomarker) increased in both CAT groups compared to placebo (P < .001). The CAT is safe in humans and a potential treatment for patients with acute myocardial infarction undergoing reperfusion therapy.