Examinando por Autor "Mellado, Marco"

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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 AG, 2017-03) Apablaza, Gastón; Montoya, Luisa; Morales-Verdejo, Cesar; Mellado, Marco; Cuellar, Mauricio; Lagos, Carlos F.; Soto-Delgado, Jorge; Chung, Hery; Pessoa-Mahana, Carlos David; Mella, Jaime
    The β3 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 β3 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 β3 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 β3 adrenergic activity is given. © 2017 by the authors.
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    Synthesis and in vitro growth inhibition of 2-allylphenol derivatives against Phythopthora cinnamomi rands
    (MDPI AG, 2019-11) Olea, Andrés F.; Espinoza, Luis; Sedan, Claudia; Thomas, Mario; Martínez, Rolando; Mellado, Marco; Carrasco, Héctor; Díaz, Katy
    Phytophthora cinnamomi is a phytopathogen that causes extensive damage in different crops, and therefore, produces important economic losses all around the world. Chemical fungicides are a key factor for the control of this disease. However, ecological and environmental considerations, as well as the appearance of strains that are resistant to commercial fungicides, have prompted the quest for new antifungal agents which are of low ecological impact. In this work, a series of new 2-allylphenol derivatives was synthesized, and their structures were confirmed by FT-IR, NMR, and MS. Some of the synthesized compounds, more specifically nitro derivatives, exhibit strong growth inhibition of P. cinnamomi with EC50 as low as 10.0 μg/mL. This level of activity is similar to that exhibited by METALAXYL MZ 58 WP, a commonly-used commercial fungicide; therefore, these compounds might be of agricultural interest due to their potential use as fungicides against P. cinnamomi. The results indicate that this activity depends on the chemical structures of the 2-allylphenol derivatives, and that it is strongly enhanced in molecules where nitro and hydroxyl groups adopt a -para configuration. These effects are discussed in terms of the electronic distribution of the aromatic ring induced by substituent groups. © 2019 by the authors.