9 results on '"Alarcón-Espósito J"'
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2. Iso-solvation effects in mixtures of ionic liquids on the kinetics of a model SNAr reaction.
- Author
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Alarcón-Espósito, J., Contreras, R., and Campodónico, P. R.
- Subjects
- *
IONIC liquids , *SOLVATION kinetics , *DINITROBENZENES - Abstract
The SNAr reaction between 1-chloro-2,4-dinitrobenzene and morpholine was used as a model system to study solvation effects in a series of mixtures involving imidazolium based ionic liquids. Iso-solvation regimes (i.e. a solvent composition regime where the solute is being solvated by approximately the same number of different solvent molecules in the mixture) are reported for the first time in ionic liquid mixtures, for 4 mixtures including [EMIM][SCN][DCN], [BMIM][DCN][BF4], [BMIM][BF4][PF6] and [BMIM][PF6][FAP]. The results show that for significant changes in composition, the rate coefficients remain approximately constant. An additional interesting result is that the mixture [BMIM][BF4][PF6] (in the proportion of 0.9 for the molar fraction of BMIMBF4) shows a slightly better kinetic performance as compared to pure BMIMBF4 and BMIMPF6. Finally, for the [EMIM][SCN][DCN] mixture, an increasing proportion of EMIMSCN with respect to EMIMDCN results in a decrease in the rate coefficient within the range of {0.1–0.75} for the molar fraction of EMIMSCN. This result may be traced to competition between the anions [SCN−] and [DCN−] towards the reaction center driven by the basicity of the reaction medium. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
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3. Analysis of the Behavior of Deep Eutectic Solvents upon Addition of Water: Its Effects over a Catalytic Reaction.
- Author
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Campodónico PR, Alarcón-Espósito J, Alcázar JJ, Olivares B, and Suárez-Rozas C
- Subjects
- Catalysis, Hydrolysis, Solvents chemistry, Biocatalysis, Kinetics, Lipase chemistry, Lipase metabolism, Water chemistry, Deep Eutectic Solvents chemistry, Fungal Proteins chemistry, Hydrogen Bonding
- Abstract
This study presents the potential role of deep eutectic solvents (DESs) in a lipase-catalyzed hydrolysis reaction as a co-solvent in an aqueous solution given by a phosphate buffer. Ammonium salts, such as choline chloride, were paired with hydrogen bond donors, such as urea, 1,2,3-propanetriol, and 1,2 propanediol. The hydrolysis of p- nitrophenyl laureate was carried out with the lipase Candida antarctica Lipase B (CALB) as a reaction model to evaluate the solvent effect and tested in different DES/buffer phosphate mixtures at different % w/w. The results showed that two mixtures of different DES at 25 % w/w were the most promising solvents, as this percentage enhanced the activities of CALB, as evidenced by its higher catalytic efficiency (kcatKM). The solvent analysis shows that the enzymatic reaction requires a reaction media rich in water molecules to enable hydrogen-bond formation from the reaction media toward the enzymatic reaction, suggesting a better interaction between the substrate and the enzyme-active site. This interaction could be attributed to high degrees of freedom influencing the enzyme conformation given by the reaction media, suggesting that CALB acquires a more restrictive structure in the presence of DES or the stabilized network given by the hydrogen bond from water molecules in the mixture improves the enzymatic activity, conferring conformational stability by solvent effects. This study offers a promising approach for applications and further perspectives on genuinely green industrial solvents.
- Published
- 2024
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4. A New Paradigm Shift in Antidepressant Therapy: From Dual-action to Multitarget-directed Ligands.
- Author
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Rodríguez-Lavado J, Alarcón-Espósito J, Mallea M, and Lorente A
- Subjects
- Antidepressive Agents pharmacology, Antidepressive Agents therapeutic use, Humans, Selective Serotonin Reuptake Inhibitors therapeutic use, Depressive Disorder, Major drug therapy
- Abstract
Major Depressive Disorder is a chronic, recurring, and potentially fatal disease, affecting up to 20% of the global population. Since the monoamine hypothesis was proposed more than 60 years ago, only a few relevant advances have been made, with very little disease course changing from a pharmacological perspective. Moreover, since the negative efficacy of novel molecules is frequently reported in studies, many pharmaceutical companies have put new studies on hold. Fortunately, relevant clinical studies are currently being performed extensively, developing immense interest among universities, research centers, and other public and private institutions. Depression is no longer considered a simple disease but a multifactorial one. New research fields are emerging, occurring a paradigm shift, such as the multi-target approach beyond monoamines. In this review, we summarize antidepressant drug discovery aiming to shed some light on the current state-of-the-art clinical and preclinical advances to face this increasingly devastating disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2022
- Full Text
- View/download PDF
5. Kinetics and Reaction Mechanism of Biothiols Involved in S N Ar Reactions: An Experimental Study.
- Author
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Campodónico PR, Alarcón-Espósito J, and Olivares B
- Abstract
Few kinetic parameters, or reaction rates, are known up to date in detail about 1-chloro and 1-fluoro-2,4-dinitrobenzene (ClDNB and FDNB, respectively) with a series of biothiols in aqueous media. These biological nucleophiles with thiol groups have been widely used as a reference in nucleophile reactivity assays due to their prevalence and cellular abundance. The main aim of this study was to elucidate the reaction mechanism based on Brönsted-type plots and reactivity patterns of the electrophile/nucleophile pairs. A complete kinetic study was performed in terms of the comparison of Brönsted-type slope parameters ( β
nuc ) for the reactions and was used for assigning the mechanism and the rate-determining step associated with the reaction route. A mass spectrometry analysis demonstrated that the nucleophilic center of the biothiols is the -SH group and there is only one kinetic product. The kinetic study suggests that the reaction mechanism might be the borderline between concerted and stepwise pathways. An amine-enol equilibrium for the most reactive nucleophiles appears to be the main determining factor controlling the nucleophilic attack in the nucleophilic aromatic substitution reactions investigated, highlighting the anionic form for these nucleophiles. This amine-enol equilibrium involves a hydrogen bond which stabilizes the intermediate species in the reaction pathway. Thus, intramolecular bonds are formed and enhance the nucleophilic strength through the contribution of the solvent surrounding the electrophile/nucleophile pairs. Finally, we highlight the importance of the formation of electrophile/nucleophile adducts that could modify structures and/or functions of biological systems with potential toxic effects. Therefore, it is essential to know all these kinetic and reactivity patterns and their incidence on other studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Campodónico, Alarcón-Espósito and Olivares.)- Published
- 2022
- Full Text
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6. Phenolic Composition and α-Glucosidase Inhibition of Leaves from Chilean Bean Landraces.
- Author
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Alarcón-Espósito J, Nina N, Theoduloz C, Burgos-Edwards A, Paillan H, and Schmeda-Hirschmann G
- Subjects
- Antioxidants chemistry, Antioxidants pharmacology, Chile, Glycoside Hydrolase Inhibitors chemistry, Glycoside Hydrolase Inhibitors pharmacology, Lipase, Phenols pharmacology, Plant Extracts chemistry, Plant Extracts pharmacology, alpha-Amylases, Fabaceae chemistry, alpha-Glucosidases metabolism
- Abstract
The MeOH:H
2 O (7:3) extracts of leaves from Chilean bean landraces were assessed for total phenolic (TP), total flavonoid (TF), total proanthocyanidin (TPA) content, antioxidant capacity (ORAC, FRAP, TEAC, CUPRAC, DPPH) and the inhibition of enzymes associated with metabolic syndrome (α-glucosidase, α-amylase, pancreatic lipase). The chemical profiles were analyzed by HPLC-DAD. Higher antioxidant activity in the ORAC and CUPRAC assay was found for the landrace Coscorrón, and the best effect in the TEAC for Sapito, respectively. The main phenolics were flavonol glycosides and caffeic acid derivatives. The extracts presented strong activity against α-glucosidase, but were inactive towards α-amylase and pancreatic lipase. The leaf extract from the Sapito landrace was fractionated to isolate the main α-glucosidase inhibitors, leading to caffeoylmalic acid with an IC50 of 0.21 μg/mL. The HPLC fingerprints of the leaves differentiate three groups of chemical profiles, according to the main phenolic content. A significant correlation was found between the α-glucosidase inhibition, the content of caffeoylmalic acid (r = -0.979) and kaempferol 3-O-β-D-glucoside (r = 0.942) in the extracts. The presence of α-glucosidase inhibitors in the leaves of Chilean beans support their potential as a source of bioactive compounds., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)- Published
- 2022
- Full Text
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7. From Hybrids to New Scaffolds: The Latest Medicinal Chemistry Goals in Multi-target Directed Ligands for Alzheimer's Disease.
- Author
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Alarcón-Espósito J, Mallea M, and Rodríguez-Lavado J
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- Aged, Amyloid beta-Peptides, Chemistry, Pharmaceutical, Cholinesterase Inhibitors, Goals, Humans, Ligands, Alzheimer Disease drug therapy, Pharmaceutical Preparations
- Abstract
Alzheimer's disease (AD) is a chronic, progressive, and fatal neurodegenerative disorder affecting cognition, behavior, and function, being one of the most common causes of mental deterioration in elderly people. Once thought as being just developed because of β amyloid depositions or neurofibrillary Tau tangles, during the last decades, numerous AD-related targets have been established, the multifactorial nature of AD became evident. In this context, the one drug-one target paradigm has resulted in being inefficient in facing AD and other disorders with complex etiology, opening the field for the emergence of the multitarget approach. In this review, we highlight the recent advances within this area, emphasizing in hybridization tools of well-known chemical scaffolds endowed with pharmacological properties concerning AD, such as curcumin-, resveratrol-, chromone- and indole-. We focus mainly on well established and incipient AD therapeutic targets, AChE, BuChE, MAOs, β-amyloid deposition, 5-HT4 and Serotonin transporter, with the aim to shed light about new insights in the AD multitarget therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2021
- Full Text
- View/download PDF
8. Synthesis, Docking, 3-D-Qsar, and Biological Assays of Novel Indole Derivatives Targeting Serotonin Transporter, Dopamine D2 Receptor, and Mao-A Enzyme: In the Pursuit for Potential Multitarget Directed Ligands.
- Author
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Cerda-Cavieres C, Quiroz G, Iturriaga-Vásquez P, Rodríguez-Lavado J, Alarcón-Espósito J, Saitz C, Pessoa-Mahana CD, Chung H, Araya-Maturana R, Mella-Raipán J, Cabezas D, Ojeda-Gómez C, Reyes-Parada M, and Pessoa-Mahana H
- Subjects
- Molecular Docking Simulation, Quantitative Structure-Activity Relationship, Receptors, Dopamine D2 genetics, Serotonin Plasma Membrane Transport Proteins genetics, Structure-Activity Relationship, Biological Assay methods, Receptors, Dopamine D2 metabolism, Serotonin Plasma Membrane Transport Proteins metabolism
- Abstract
A series of 27 compounds of general structure 2,3-dihydro-benzo[1,4]oxazin-4-yl)-2-{4-[3-(1 H -3indolyl)-propyl]-1-piperazinyl}-ethanamides, Series I: 7 ( a - o ) and (2-{4-[3-(1 H -3-indolyl)-propyl]-1-piperazinyl}-acetylamine)- N -(2-morfolin-4-yl-ethyl)-fluorinated benzamides Series II: 13 ( a - l ) were synthesized and evaluated as novel multitarget ligands towards dopamine D
2 receptor, serotonin transporter (SERT), and monoamine oxidase-A (MAO-A) directed to the management of major depressive disorder (MDD). All the assayed compounds showed affinity for SERT in the nanomolar range, with five of them displaying K i values from 5 to 10 nM. Compounds 7k , K i = 5.63 ± 0.82 nM, and 13c , K i = 6.85 ± 0.19 nM, showed the highest potencies. The affinities for D2 ranged from micro to nanomolar, while MAO-A inhibition was more discrete. Nevertheless, compounds 7m and 7n showed affinities for the D2 receptor in the nanomolar range ( 7n : K i = 307 ± 6 nM and 7m : K i = 593 ± 62 nM). Compound 7n was the only derivative displaying comparable affinities for SERT and D2 receptor (D2 /SERT ratio = 3.6) and could be considered as a multitarget lead for further optimization. In addition, docking studies aimed to rationalize the molecular interactions and binding modes of the designed compounds in the most relevant protein targets were carried out. Furthermore, in order to obtain information on the structure-activity relationship of the synthesized series, a 3-D-QSAR CoMFA and CoMSIA study was conducted and validated internally and externally (q2 = 0.625, 0.523 for CoMFA and CoMSIA and r2 ncv = 0.967, 0.959 for CoMFA and CoMSIA, respectively).- Published
- 2020
- Full Text
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9. Gutmann's Donor Numbers Correctly Assess the Effect of the Solvent on the Kinetics of SN Ar Reactions in Ionic Liquids.
- Author
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Alarcón-Espósito J, Contreras R, Tapia RA, and Campodónico PR
- Abstract
We report an experimental study on the effect of solvents on the model SN Ar reaction between 1-chloro-2,4-dinitrobenzene and morpholine in a series of pure ionic liquids (IL). A significant catalytic effect is observed with reference to the same reaction run in water, acetonitrile, and other conventional solvents. The series of IL considered include the anions, NTf2 (-) , DCN(-) , SCN(-) , CF3 SO3 (-) , PF6 (-) , and FAP(-) with the series of cations 1-butyl-3-methyl-imidazolium ([BMIM](+) ), 1-ethyl-3-methyl-imidazolium ([EMIM](+) ), 1-butyl-2,3-dimethyl-imidazolium ([BM2 IM](+) ), and 1-butyl-1-methyl-pyrrolidinium ([BMPyr](+) ). The observed solvent effects can be attributed to an "anion effect". The anion effect appears related to the anion size (polarizability) and their hydrogen-bonding (HB) abilities to the substrate. These results have been confirmed by performing a comparison of the rate constants with Gutmann's donicity numbers (DNs). The good correlation between rate constants and DN emphasizes the major role of charge transfer from the anion to the substrate., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2016
- Full Text
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