Examinando por Autor "Cuellar, Mauricio"

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    Combined 3D-QSAR and docking analysis for the design and synthesis of chalcones as potent and selective monoamine oxidase B inhibitors
    (Elsevier, 2021) Mellado, Marco; González, César; Mella, Jaime; Aguilar, Luis F.; Viña, Dolores; Uriarte, Eugenio; Cuellar, Mauricio; Matos, Maria J.
    Monoamine oxidases (MAOs) are important targets in medicinal chemistry, as their inhibition may change the levels of different neurotransmitters in the brain, and also the production of oxidative stress species. New chemical entities able to interact selectively with one of the MAO isoforms are being extensively studied, and chalcones proved to be promising molecules. In the current work, we focused our attention on the understanding of theoretical models that may predict the MAO-B activity and selectivity of new chalcones. 3D-QSAR models, in particular CoMFA and CoMSIA, and docking simulations analysis have been carried out, and their successful implementation was corroborated by studying twenty-three synthetized chalcones (151–173) based on the generated information. All the synthetized molecules proved to inhibit MAO-B, being ten out of them MAO-B potent and selective inhibitors, with IC50 against this isoform in the nanomolar range, being (E)-3-(4-hydroxyphenyl)-1-(2,2-dimethylchroman-6-yl)prop-2-en-1-one (152) the best MAO-B inhibitor (IC50 of 170 nM). Docking simulations on both MAO-A and MAO-B binding pockets, using compound 152, were carried out. Calculated affinity energy for the MAO-A was +2.3 Kcal/mol, and for the MAO-B was −10.3 Kcal/mol, justifying the MAO-B high selectivity of these compounds. Both theoretical and experimental structure–activity relationship studies were performed, and substitution patterns were established to increase MAO-B selectivity and inhibitory efficacy. Therefore, we proved that both 3D-QSAR models and molecular docking approaches enhance the probability of finding new potent and selective MAO-B inhibitors, avoiding time-consuming and costly synthesis and biological evaluations.
  • Miniatura
    Ítem
    Nutritional analysis of lluteño maize and fatty acids characterization in modern and ancient samples from northern Chile
    (Asociación Interciencia, 2020) Ogalde, Juan Pablo; Arriaza, Bernardo; Cuellar, Mauricio
    We present a food quality evaluation of Zea mays L. amylacea from Lluta Valley, northern Chile, a species with important nutritional qualities for historic and current populations in the area. Studies were made of proximal analyses, antioxidant activity, and characterization of the fatty acids fraction. Also, the fatty acids fraction of six ancient maize samples were studied, searching for possible archaeometric markers. The results of the proximal analysis show that the modern Lluteño maize has a high carbohydrates and protein content, low moisture, high ash residue and low antioxidant activity (free radical scavenging). The oleic and linoleic fatty acids show the highest concentrations in Lluteño maize. The presence of omega-6 and omega-9 present in the maize could provide health benefits againstdiseases such as type II diabetes and cardiovascular diseases. Finally, the fatty acid distribution of the ancient maize samplescluster in two categories, one of which was similar to the modern Lluteño maize. Thus, the fatty acid fraction can be considered in the future to investigate the antiquity and evolution of Lluteño maize, and his influence on the health of the local populations.
  • Miniatura
    Ítem
    Synthesis of New Brassinosteroid 24-Norcholane Type Analogs Conjugated in C-3 with Benzoate Groups
    (MDPI, 2021) Ferrer, Karoll; Díaz, Katy; Kvasnica, Miroslav; Olea, Andrés F.; Cuellar, Mauricio; Espinoza, Luis
    The metabolism of brassinosteroid leads to structural modifications in the ring skeleton or the side alkyl chain. The esterification and glycosylation at C-3 are the most common metabolic pathways, and it has been suggested that conjugate brassinosteroids are less active or inactive. In this way, plants regulate the content of active brassinosteroids. In this work, the synthesis of brassinosteroid 24-norcholane type analogs conjugated at C-3 with benzoate groups, carrying electron donor and electron attractant substituents on the aromatic ring, is described. Additionally, their growth-promoting activities were evaluated using the Rice Lamina Inclination Test (RLIT) and compared with that exhibited by brassinolide (used as positive control) and non-conjugated analogs. The results indicate that at the lowest tested concentrations (10−8–10−7 M), all analogs conjugated at C-3 exhibit similar or higher activities than brassinolide, and the diasteroisomers with S configuration at C-22 are the more active ones. Increasing concentration (10−6 M) reduces the biological activities of analogs as compared to brassinolide.