Browsing by Author "Areche, Carlos"

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    An unusual mulinane diterpenoid from the Chilean plant Azorella trifurcata (Gaertn) Pers
    (2014) Areche, Carlos; Sepulveda, Beatriz; San Martin, Aurelio; Garcia-Beltran, Olimpo; Simirgiotis, Mario; Canete, Alvaro
    Four new mulinane-type diterpenoids besides the known compounds mulin-11,13-dien-20-oic acid, 13 alpha-hydroxyazorellane, 13 beta-hydroxyazorellane, mulinolic acid, azorellanol, and mulin-11,13-dien-18-acetoxy-16,20-dioic acid were isolated from the Chilean plant Azorella trifurcata. One of the new metabolites isolated, 7 alpha-acetoxy-9-epi-13 beta-hydroxymulinane, possesses a new trans-syn-trans arrangement in a tricyclic ring system not previously encountered in nature. Among the mulinane diterpenoids isolated, mulin-11,13-dien-20-oic acid showed the gastroprotective effect on HCl-EtOH-induced gastric lesions in mice (ED50 = 55mg kg(-1)). Regarding the mode of gastroprotective action for this active compound, its effect was reduced by pre-treatment of the mice with indomethacin and N-ethylmaleimide, suggesting that prostaglandins and sulfhydryl compounds are positively involved in the gastroprotective activity using this model.
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    Coumarin-Chalcone Hybrids as Inhibitors of MAO-B: Biological Activity and In Silico Studies
    (2021) Moya-Alvarado, Guillermo; Yanez, Osvaldo; Morales, Nicole; Gonzalez-Gonzalez, Angelica; Areche, Carlos; Nunez, Marco Tulio; Fierro, Angelica; Garcia-Beltran, Olimpo
    Fourteen coumarin-derived compounds modified at the C3 carbon of coumarin with an alpha,beta-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 mu M. 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.
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    Further mulinane diterpenoids from Azorella compacta
    (2013) Areche, Carlos; Rojas Álvarez, Francisca; Campos Briones, Carolina; Lima, Carlos; Pérez Hernández, Edwin Gregorio; Sepúlveda, Beatriz
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    Rosmarinic acid turned α-syn oligomers into non-toxic species preserving microtubules in Raw 264.7 cells
    (2024) Flores, Nicolás; Rivillas-Acevedo, Lina; Caballero, Julio; Melo, Francisco; Caballero, Leonardo; Areche, Carlos; Fuentealba Patiño, Denis Alberto; Aguilar, Felipe; Cornejo, Alberto
    Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide, and the therapeutic is focused on several approaches including the inhibition of fibril formation by small compounds, avoiding the formation of cytotoxic oligomers. Thus, we decided to explore the capacity of compounds carrying catechol moieties to inhibit the progression of α-synuclein. Overall, the compounds rosmarinic acid (1), carnosic acid (2), carnosol (3), epiisorosmanol (4), and rosmanol (5) avoid the progression of fibril formation assessed by Thiofavine T (ThT), and atomic force microscopy images showed that morphology is influenced for the actions of compounds over fibrillization. Moreover, ITC experiments showed a Kd varying from 28 to 51 µM, the ΔG showed that the reaction between compounds and α-syn is spontaneous, and ΔH is associated with an exothermic reaction, suggesting the interactions of hydrogen bonds among compounds and α-syn. Docking experiments reinforce this idea showing the intermolecular interactions are mostly hydrogen bonding within the sites 2, 9, and 3/13 of α-synuclein, and compounds 1 and 5. Thus, compound 1, rosmarinic acid, interestingly interacts better with site 9 through catechol and Lysines. In cultured Raw 264. 7 cells, the presence of compounds showed that most of them can promote cell differentiation, especially rosmarinic acid, and rosmanol, both preserving tubulin cytoskeleton. However, once we evaluated whether or not the aggregates pre-treated with compounds could prevent the disruption of microtubules of Raw 264.7 cells, only pre-treated aggregates with rosmarinic acid prevented the disruption of the cytoskeleton. Altogether, we showed that especially rosmarinic acid not only inhibits α-syn but stabilizes the remaining aggregates turning them into not-toxic to Raw 264.7 cells suggesting a main role in cell survival and antigen processing in response to external α-syn aggregates.