Browsing by Author "Zapata-Torres, Gerald"

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    5-HT2 Receptor Subfamily and the Halogen Bond Promise
    (2021) Fierro, Angelica; Matthies, Douglas J.; Cassels, Bruce K.; Jaque, Pablo; Zapata-Torres, Gerald
    The binding of C-4-halogenated 1-(4-X-2,5-dimethoxyphenyl)-2-aminopropane (DOX) serotonin agonist psychedelics at all three 5-HT2 receptor subtypes is up to two orders of magnitude stronger for X = Cl, Br, or I (but not F) than when C-4 bears a hydrogen atom and more than expected from their hydrophobicities. Our docking and molecular dynamics simulations agree with the fact that increasing the polarizability of halogens results in halogen-oxygen distances to specific backbone C=O groups, and C-X center dot center dot center dot O angles, in ranges expected for halogen bonds (XBs), which could contribute to the high affinities observed. Good linear correlations are found for each receptor type, indicating that the binding pocketl-igand affinity is enhanced as the XB interaction becomes stronger (i.e., I approximate to Br > Cl > F). It is also striking to note how the linear equations unveil that the receptor's response on the strength of the XB interaction is quite similar among 5-HT2A and 5-HT2C, whereas the 5-HT2B's sensitivity is less. The calculated dipole polarizabilities in the binding pocket of the receptors reflect the experimental affinity values, indicating that less-polarizable and harder binding sites are more prone to XB formation.
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    Influence of Protonation on Substrate and Inhibitor Interactions at the Active Site of Human Monoamine Oxidase-A
    (2012) Zapata-Torres, Gerald; Fierro Huerta, Angélica; Miranda-Rojas, Sebastian; Guajardo, Carlos; Saez-Briones, Patricio; Salgado, J. Cristian; Celis-Barros, Cristian
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    Interaction of LD14 and TiO2 in dye-sensitized solar-cells (DSSC) : A density functional theory study
    (2015) Mendizabal, Fernando; Lopéz, Alfredo; Arratia Pérez, Ramiro; Zapata-Torres, Gerald
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    Synthesis, docking and pharmacological evaluation of novel homo- and hetero-bis 3-piperazinylpropylindole derivatives at SERT and 5-HT1A receptor
    (2013) Pessoa-Mahana, Hernan; Gonzalez-Lira, Christian; Fierro, Angelica; Zapata-Torres, Gerald; David Pessoa-Mahana, C.; Ortiz-Severin, Javiera; Iturriaga-Vasquez, Patricio; Reyes-Parada, Miguel; Silva-Matus, Paul; Saitz-Barria, Claudio; Araya-Maturana, Ramiro
    A series of 3-(3-(4-(3-(1H-indol-3-yl)propyl)piperazin-1-yl)propyl)-1H-indole derivatives (3a-d and 5a-f) as homo-and hetero-bis-ligands, were synthesized and evaluated for in vitro affinity at the serotonin transporter (SERT) and the 5-HT1A receptor. Compounds 5b and 5f showed nanomolar affinities for both targets. The experimental data were rationalized according to results obtained from docking experiments. These findings are in agreement with our proposal that bis-indole derivatives can bind both targets, and might serve as leads in the quest of ligands endowed with a dual mechanism of action. (C) 2013 Elsevier Ltd. All rights reserved.