Examinando por Autor "Lagos, C.F."

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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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    Eplerenone Implantation Improved Adipose Dysfunction Averting RAAS Activation and Cell Division
    (Frontiers Media S.A., 2020-04) Vecchiola, A.; Fuentes, C.A.; Solar, I.; Lagos, C.F.; Opazo, M.C.; Muñoz-Durango, N.; Riedel, C.A.; Owen, G.I.; Kalergis, A.M.; Fardella, C.E.
    Introduction: Mineralocorticoid receptor (MR) activation within adipose tissue, triggers inflammation and metabolic syndrome development. The pharmacological blockade of MR provides beneficial effects for adipose tissue. Our study evaluates the impact of eplerenone implantation upon obesity. Experimental approach: A group of mice with implanted placebo pellets were fed using two types of diet, a normal (ND) or a high fat (HFD) diet. Additionally, a group of mice fed HFD were implanted with an eplerenone pellet. Metabolic and biochemical parameters were assessed in each animal group. Adipocyte size and lipid accumulation were investigated in the liver and adipose tissue. We evaluated the components of renin-angiotensin-aldosterone system (RAAS) locally in adipose tissue. Key results: Eplerenone reduced HFD-induced body weight gain, fasting glucose levels, fat accumulation, HFD-induced adipocyte size and liver lipid accumulation and improved glucose tolerance. In the adipose tissue, HFD significantly increased the mRNA levels of the RAAS molecules relative to the ND group. Eplerenone lowered RAAS mRNA levels, components of lipid metabolism and markers of inflammation in HFD-fed animals. Conclusion: MR antagonism with eplerenone diminishes insulin resistance that is related to obesity partly via a reduction of RAAS activation, inflammatory progression and cytokines induction. This suggests that eplerenone should be further studied as a therapeutic option for obesity and overweight. © Copyright © 2020 Vecchiola, Fuentes, Solar, Lagos, Opazo, Muñoz-Durango, Riedel, Owen, Kalergis and Fardella.