Examinando por Autor "Cuellar, M."

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    2D-QSAR and 3D-QSAR/CoMSIA studies on a series of (R)-2-((2-(1H-Indol-2-yl)ethyl)amino)-1-phenylethan-1-ol with human β3-adrenergic activity
    (MDPI, 2017-03) Apablaza, G.; Montoya, L.; Morales-Verdejo, C.; Mellado, M.; Cuellar, M.; Lagos, C.F.; Soto-Delgado, J.; Chung, H.; Pessoa-Mahana, C.D.; Mella, J.
    The beta(3) adrenergic receptor is raising as an important drug target for the treatment of pathologies such as diabetes, obesity, depression, and cardiac diseases among others. Several attempts to obtain selective and high affinity ligands have been made. Currently, Mirabegron is the only available drug on the market that targets this receptor approved for the treatment of overactive bladder. However, the FDA (Food and Drug Administration) in USA and the MHRA (Medicines and Healthcare products Regulatory Agency) in UK have made reports of potentially life-threatening side effects associated with the administration of Mirabegron, casting doubts on the continuity of this compound. Therefore, it is of utmost importance to gather information for the rational design and synthesis of new beta(3) adrenergic ligands. Herein, we present the first combined 2D-QSAR (two-dimensional Quantitative Structure-Activity Relationship) and 3D-QSAR/CoMSIA (three-dimensional Quantitative Structure-Activity Relationship/Comparative Molecular Similarity Index Analysis) study on a series of potent (3) adrenergic agonists of indole-alkylamine structure. We found a series of changes that can be made in the steric, hydrogen-bond donor and acceptor, lipophilicity and molar refractivity properties of the compounds to generate new promising molecules. Finally, based on our analysis, a summary and a regiospecific description of the requirements for improving beta(3) adrenergic activity is given.
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    Biopesticide activity from drimanic compounds to control tomato pathogens
    (MDPI AG, 2018-08) Montenegro, I.; Madrid, A.; Cuellar, M.; Seeger, M.; Alfaro, J.F.; Besoain, X.; Martínez, J.P.; Ramirez, I.; Olguín, Y.; Valenzuela, M.
    Tomato crops can be affected by several infectious diseases produced by bacteria, fungi, and oomycetes. Four phytopathogens are of special concern because of the major economic losses they generate worldwide in tomato production; Clavibacter michiganensis subsp. michiganensis and Pseudomonas syringae pv. tomato, causative agents behind two highly destructive diseases, bacterial canker and bacterial speck, respectively; fungus Fusarium oxysporum f. sp. lycopersici that causes Fusarium Wilt, which strongly affects tomato crops; and finally, Phytophthora spp., which affect both potato and tomato crops. Polygodial (1), drimenol (2), isonordrimenone (3), and nordrimenone (4) were studied against these four phytopathogenic microorganisms. Among them, compound 1, obtained from Drimys winteri Forst, and synthetic compound 4 are shown here to have potent activity. Most promisingly, the results showed that compounds 1 and 4 affect Clavibacter michiganensis growth at minimal inhibitory concentrations (MIC) values of 16 and 32 μg/mL, respectively, and high antimycotic activity against Fusarium oxysporum and Phytophthora spp. with MIC of 64 μg/mL. The results of the present study suggest novel treatment alternatives with drimane compounds against bacterial and fungal plant pathogens. © 2018 by the authors.
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    Eugenol and its Synthetic Analogues Inhibit Cell Growth of Human Cancer Cells (Part I)
    (Sociedad Brasilera de Química, 2008) Carrasco, H.; Espinoza, L.; Cardile, V.; Gallardo, C.; Cardona, W.; Lombardo, L.; Catálan, K.; Cuellar, M.; Russo, A.
    Eugenol (4-allyl-2-methoxyphenol) (1) has been reported to possess antioxidant and anticancer properties. In an attempt to enhance intrinsic activity of this natural compound, some derivatives were synthesized. Eugenol was extracted from cloves oil and further, the eugenol analogues (2-6) were obtained through acetylation and nitration reactions. Eugenol (1) and its analogues (2-6) were examined by in vitro model of cancer using two human cancer cell lines: DU-145 (androgen-insensitive prostate cancer cells) and KB (oral squamous carcinoma cells). Cell viability, by tetrazolium salts assay, was measured. Lactic dehydrogenase (LDH) release was also investigated to evaluate the presence of cell toxicity as a result of cell disruption, subsequent to membrane rupture. In the examined cancer cells, all compounds showed cell-growth inhibition activity. The obtained results demonstrate that the compounds 5-allyl-3-nitrobenzene-1,2-diol (3) and 4-allyl-2-methoxy-5-nitrophenyl acetate (5) were significantly (p < 0,001) more active than eugenol, with IC50 values in DU-145 cells of 19.02 x 10-6 and 21.5 × 10-6 mol L-1, respectively, and in KB cells of 18.11 × 10-6 and 21.26 × 10-6 mol L-1, respectively, suggesting that the presence of nitro and hydroxyl groups could be important in the activity of these compounds. In addition, our results seem to indicate that apoptotic cell demise appears to be induced in KB and DU-145 cells. In fact, in our experimental conditions, no statistically significant increase in LDH release was observed in cancer cells treated with eugenol and its analogues.
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    Phenolics, depsides and triterpenes from the chilean lichen pseudocyphellaria nudata (zahlbr.) D.J. Galloway
    (Sociedad Chilena de Química, 2008) Cuellar, M.; Quilhot, W.; Rubio, C.; Soto, C.; Espinoza, L.
    The lichen Pseudocyphellaria nudata is a species endemic to southern South América. From the lichen tallus, methyl orsellinate, 2-methoxy-3,6-dimethyl-4-hydroxybenzaldehyde, methyl-evernate, tenuiorin, hopan-6ß,22-diol and hopan-6α,76,22-triol were isolated and identified as the main lichen constituents. This is the first report of the occurrence of 2-methoxy-3,6-dimethyl-4-hydroxybenzaldehyde in lichens.