Examinando por Autor "Morales, Nicole"
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- PublicaciónSólo datosCoumarin-Chalcone Hybrids as Inhibitors of MAO-B: Biological Activity and In Silico Studies(Molecules, 2021-04-22) Moya-Alvarado, Guillermo; Yañez, Osvaldo; Morales, Nicole; González-González, Angélica; Areche, Carlos; Núñez, Marco Tulio; Fierro, Angélica; García Beltrán, OlimpoFourteen coumarin-derived compounds modified at the C3 carbon of coumarin with an α,β-unsaturated ketone were synthesized. These compounds may be designated as chalcocoumarins (3-cinnamoyl-2H-chromen-2-ones). Both chalcones and coumarins are recognized scaffolds in medicinal chemistry, showing diverse biological and pharmacological properties among which neuroprotective activities and multiple enzyme inhibition, including mitochondrial enzyme systems, stand out. The evaluation of monoamine oxidase B (MAO-B) inhibitors has aroused considerable interest as therapeutic agents for neurodegenerative diseases such as Parkinson’s. Of the fourteen chalcocumarins evaluated here against MAO-B, ChC4 showed the strongest activity in vitro, with IC50 = 0.76 ± 0.08 µM. Computational docking, molecular dynamics and MM/GBSA studies, confirm that ChC4 binds very stably to the active rMAO-B site, explaining the experimental inhibition data.
- PublicaciónSólo datosDiscovery two potent and new inhibitors of 15-lipoxygenase: (E)-3-((3,4-dihydroxybenzylidene) amino)-7-hydroxy-2H-chromen-2-one and (E)-O-(4-(((7-hydroxy-2-oxo-2H-chromen-3-yl) imino)methine) phenyl)dimethylcarbamothioate(Medicinal Chemistry Research, 2017-10-30) Núñez, Carolina; Morales, Nicole; García-Beltrán, Olimpo; Mascayano, Carolina; Fierro, AngélicaThe mechanisms of action and structural determinants of lipoxygenases inhibitors have been explored on several occasions, but many questions remain unanswered, especially about the differences of the inhibition mechanisms and their effect on the selectivity of lipoxygenases isoenzymes. Thus, REDOX mechanism has been proposed in this research to clarify the lipoxygenases inhibition by coumarins derivates on 15-sLOX. A series of fifteen coumarin derivatives were synthetized and evaluated as 15-lipoxygenase inhibitors. The results showed that some molecules had submicromolar activities and compete with the substrate as we observed by kinetic studies. The most relevant and interesting result was found for compound 6 who showed an inhibitory activity comparable to nordihydroguaiaretic acid a potent and REDOX inhibitor of lipoxygenases (0.17 and 0.29 μM, respectively). Finally, the docking and molecular dynamics studies showed that the better ligands were accommodated into the binding site being related with those obtained biological data. In addition, our findings contribute at the understanding of inhibitor structural requirements and elucidate the inhibition mechanism of cumarin derivatives on 15-sLOX. Thus, we point to new parameters for the future design of new ligands with potential therapeutic utility where are involved the lipoxygenases enzymes.