Browsing by Author "Mascayano, Carolina"

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    Effect of substituents and chain length in amino-1,4-naphthoquinones on glutathione-S-transferase inhibition: molecular docking and electrochemical perspectives: a structure-activity study
    (2022) Faundes, Judith; Munoz-Osses, Michelle; Morales, Pilar; Tasca, Federico; Zuniga Loyola, Cesar; Faundez, Mario; Mascayano, Carolina; Ibacache, Juana A.
    In this study, new homodimers and monoamination products based on the pharmacophore amino-1,4-naphthoquinone were synthesized. To perform a structure-activity study, three precursor quinones (2,3-dichloro-1,4-naphthoquinone, 1,4-naphthoquinone, and 2-hydroxy-1,4-naphthoquinone) and four diamines (4,40-diaminodiphenylmethane, 4,40-ethylenedianiline, ethylenediamine and 1,3-diaminopropane) were used. The reactions of the compounds were accomplished in the presence or the absence of Lewis acid as a catalyst. The new derivatives were evaluated as potential inhibitors of the enzyme glutathione-S-transferase (GST) by conjugating reduced glutathione (GSH) with the substrate 1-chloro-2,4-dinitrobenzene (CDNB). The study of the GST activity showed a clear structure-activity relationship in which the chlorinated compound 8 was the best inhibitor, with inhibition percentage values of 57%, being in the inhibition range as other GST inhibitors such as hexachlorophene and ethacrynic acid. These experimental results are consistent with molecular docking studies which show that compound 8 binds to the enzyme close to the catalytic site (G-site) and the chlorine group shows up to be essential for the stability of the ligand. Additionally, from the in silico exploration, a directly proportional trend between lipophilicity and enzyme affinity was noted, correlating with the experimental results of GST activity where the chlorine atom contributes positively to it. Finally, the electrochemical characterization provided another significant insight: the compounds with higher formal potential values (E-0) had the electron-withdrawing group chlorine being the most active against GST.
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    Structural analysis and molecular docking of trypanocidal aryloxy-quinones in trypanothione and glutathione reductases: a comparison with biochemical data
    (2017) Vera, Brenda; Vázquez, Karina; Mascayano, Carolina; Tapia Apati, Ricardo; Espinosa, Victoria; Soto, Jorge Delgado; Salas Sánchez, Cristián Osvaldo; Paulino, Margot
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    The Thioredoxin Fold Protein (TFP2) from Extreme Acidophilic Leptospirillum sp. CF-1 Is a Chaperedoxin-like Protein That Prevents the Aggregation of Proteins under Oxidative Stress
    (2024) Munoz-Villagran, Claudia; Acevedo-Arbunic, Javiera; Haertig, Elisabeth; Issotta, Francisco; Mascayano, Carolina; Jahn, Dieter; Jahn, Martina; Levican, Gloria
    Extreme acidophilic bacteria like Leptospirillum sp. require an efficient enzyme system to counteract strong oxygen stress conditions in their natural habitat. The genome of Leptospirillum sp. CF-1 encodes the thioredoxin-fold protein TFP2, which exhibits a high structural similarity to the thioredoxin domain of E. coli CnoX. CnoX from Escherichia coli is a chaperedoxin that protects protein substrates from oxidative stress conditions using its holdase function and a subsequent transfer to foldase chaperones for refolding. Recombinantly produced and purified Leptospirillum sp. TFP2 possesses both thioredoxin and chaperone holdase activities in vitro. It can be reduced by thioredoxin reductase (TrxR). The tfp2 gene co-locates with genes for the chaperone foldase GroES/EL on the chromosome. The "tfp2 cluster" (ctpA-groES-groEL-hyp-tfp2-recN) was found between 1.9 and 8.8-fold transcriptionally up-regulated in response to 1 mM hydrogen peroxide (H2O2). Leptospirillum sp. tfp2 heterologously expressed in E. coli wild type and cnoX mutant strains lead to an increased tolerance of these E. coli strains to H2O2 and significantly reduced intracellular protein aggregates. Finally, a proteomic analysis of protein aggregates produced in E. coli upon exposition to oxidative stress with 4 mM H2O2, showed that Leptospirillum sp. tfp2 expression caused a significant decrease in the aggregation of 124 proteins belonging to fifteen different metabolic categories. These included several known substrates of DnaK and GroEL/ES. These findings demonstrate that Leptospirillum sp. TFP2 is a chaperedoxin-like protein, acting as a key player in the control of cellular proteostasis under highly oxidative conditions that prevail in extreme acidic environments.