Examinando por Autor "Yáñez, Osvaldo"
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Ítem Chemical composition, antioxidant, antimicrobial and antiproliferative activity of Laureliopsis philippiana essential oil of Chile, study in vitro and in silico(Elsevier B.V., 2022-12) Bruna, Flavia; Fernández, Katia; Urrejola, Felipe; Touma, Jorge; Navarro, Myriam; Sepúlveda, Betsabet; Larrazabal Fuentes, María; Paredes, Adrián; Neira, Iván; Ferrando, Matías; Osorio, Manuel; Yáñez, Osvaldo; Bravo, JessicaChilean Laureliopsis philippiana has been used in traditional medicine by the Mapuche and their ancestors. To evaluate its pharmacological activity, Laureliopsis philippiana leaf essential oil extract (LP_EO) was chemically and biologically characterized in the present study. In vitro antioxidant potential was analyzed, and antitumor activity was evaluated in non-tumor and tumor cell culture lines. Caenorhabditis elegans was used as a model for evaluating toxicity, and the chemical composition of the essential oil was analyzed using gas chromatography–mass spectrometry. The oil contains six major monoterpenes: eucalyptol (27.7 %), linalool (27.6 %), isozaphrol (19.5 %), isohomogenol (12.6 %), α-terpineol (7.7 %), and eudesmol (4.8 %). Based on quantum mechanical calculations, isosafrole and isohomogenol conferred in vitro antioxidant and antimicrobial activity to LP_EO. In addition, LP_EO showed antimicrobial activity against clinical Helicobacter pylori isolates (MIC 64 and MBC > 128 μg·mL−1), Staphylococcus aureus (MIC 32 and MBC > 64 μg·mL−1), Escherichia coli (MIC 8 and MBC 16 μg·mL−1) and Candida albicans (MIC 64 and > 128 μg·mL−1). LP_EO could selectively inhibit the proliferation of epithelial tumor cell lines but showed low toxicity against Caenorhabditis elegans (0.39 to 1.56 μg·mL−1). Therefore, LP_EO may be used as a source of bioactive compounds in novel pharmacological treatments for veterinary and human application, cosmetics, or sanitation. © 2022 The AuthorsÍtem Electronic Transmutation Concept: Is the Inverse Process Possible? An Evaluation of Main Group Compounds(American Chemical Society, 2023-01) Báez-Grez, Rodrigo; Yáñez, Osvaldo; Pino-Rios, RicardoThe electronic transmutation (ET) concept states that when an element with atomic number Z gains an electron, it transmutes into a Z + 1 element, leading to species that possess similar chemical bonding patterns and geometric structures regarding the original (Z + 1) element. In this work, the opposite concept, that is, the inverse ET, is assessed. For this purpose, several main group compounds have been analyzed in terms of the adaptive natural density partitioning. The obtained results suggest that when an atom Z loses an electron, it transmutes into a Z − 1 atom, acquiring its geometrical structure and bonding pattern. © 2023 The Authors.Ítem Search for Novel Potent Inhibitors of the SARS-CoV-2 Papain-like Enzyme: A Computational Biochemistry Approach(MDPI, 2022-08) Osorio, Manuel I.; Yáñez, Osvaldo; Gallardo, Mauricio; Zuñiga Bustos, Matías; Mulia Rodríguez, Jorge; López Rendón, Roberto; García Beltrán, Olimpo; González Nilo, Fernando; Pérez Donoso, José M.The rapid emergence and spread of new variants of coronavirus type 2, as well as the emergence of zoonotic viruses, highlights the need for methodologies that contribute to the search for new pharmacological treatments. In the present work, we searched for new SARS-CoV-2 papain-like protease inhibitors in the PubChem database, which has more than 100 million compounds. Based on the ligand efficacy index obtained by molecular docking, 500 compounds with higher affinity than another experimentally tested inhibitor were selected. Finally, the seven compounds with ADME parameters within the acceptable range for such a drug were selected. Next, molecular dynamics simulation studies at 200 ns, ΔG calculations using molecular mechanics with generalized Born and surface solvation, and quantum mechanical calculations were performed with the selected compounds. Using this in silico protocol, seven papain-like protease inhibitors are proposed: three compounds with similar free energy (D28, D04, and D59) and three compounds with higher binding free energy (D60, D99, and D06) than the experimentally tested inhibitor, plus one compound (D24) that could bind to the ubiquitin-binding region and reduce the effect on the host immune system. The proposed compounds could be used in in vitro assays, and the described protocol could be used for smart drug design. © 2022 by the authors.Ítem Steady State Kinetics for Enzymes with Multiple Binding Sites Upstream of the Catalytic Site(MDPI, 2024-12-12) Osorio, Manuel I.; Petrache, Mircea; Salinas, Dino G.; Valenzuela-Ibaceta, Felipe; González-Nilo, Fernando; Tiznado, William; Pérez-Donoso, José M.; Bravo, Denisse; Yáñez, OsvaldoThe Michaelis–Menten mechanism, which describes the binding of a substrate to an enzyme, is a simplification of the process on a molecular scale. A more detailed model should include the binding of the substrate to precatalytic binding sites (PCBSs) prior to the transition to the catalytic site. Our work shows that the incorporation of PCBSs, in steady-state conditions, generates a Michaelis–Menten-type expression, in which the kinetic parameters KM and Vmax adopt more complex expressions than in the model without PCBSs. The equations governing reaction kinetics can be seen as generalized symmetries, relative to time translation actions over the state space of the underlying chemical system. The study of their structure and defining parameters can be interpreted as looking for invariants associated with these time evolution actions. The expression of (Formula presented.) decreases as the number of PCBSs increases, while (Formula presented.) reaches a minimum when the first PCBSs are incorporated into the model. To evaluate the trend of the dynamic behavior of the system, numerical simulations were performed based on schemes with different numbers of PCBSs and six conditions of kinetic constants. From these simulations, with equal kinetic constants for the formation of the Substrate/PCBS complex, it is observed that (Formula presented.) and (Formula presented.) are lower than those obtained with the Michaelis–Menten model. For the model with PCBSs, the (Formula presented.) reaches a minimum at one PCBS and that value is maintained for all of the systems evaluated. Since (Formula presented.) decreases with the number of PCBSs, the catalytic efficiency increases for enzymes fitting this model. All of these observations are consistent with the general equation obtained. This study allows us to explain, on the basis of the PCBS to (Formula presented.) and (Formula presented.) ratios, the effect on enzyme parameters due to mutations far from the catalytic site, at sites involved in the first enzyme/substrate interaction. In addition, it incorporates a new mechanism of enzyme activity regulation that could be fundamental to search for new activity-modulating sites or for the design of mutants with modified enzyme parameters.Ítem Structural Factors That Determine the Activity of the Xenobiotic Reductase B Enzyme from Pseudomonas putida on Nitroaromatic Compounds(MDPI, 2023-01) Osorio, Manuel I.; Bruna, Nicolás; García, Víctor; González-Rodríguez, Lisdelys; Leal, Matías S.; Salgado, Francisco; Vargas-Reyes, Matías; González-Nilo, Fernando; Pérez-Donoso, José M.; Yáñez, OsvaldoXenobiotic reductase B (XenB) catalyzes the reduction of the aromatic ring or nitro groups of nitroaromatic compounds with methyl, amino or hydroxyl radicals. This reaction is of biotechnological interest for bioremediation, the reuse of industrial waste or the activation of prodrugs. However, the structural factors that explain the binding of XenB to different substrates are unknown. Molecular dynamics simulations and quantum mechanical calculations were performed to identify the residues involved in the formation and stabilization of the enzyme/substrate complex and to explain the use of different substrates by this enzyme. Our results show that Tyr65 and Tyr335 residues stabilize the ligands through hydrophobic interactions mediated by the aromatic rings of these aminoacids. The higher XenB activity determined with the substrates 1,3,5-trinitrobenzene and 2,4,6-trinitrotoluene is consistent with the lower energy of the highest occupied molecular orbital (LUMO) orbitals and a lower energy of the homo orbital (LUMO), which favors electrophile and nucleophilic activity, respectively. The electrostatic potential maps of these compounds suggest that the bonding requires a large hydrophobic region in the aromatic ring, which is promoted by substituents in ortho and para positions. These results are consistent with experimental data and could be used to propose point mutations that allow this enzyme to process new molecules of biotechnological interest.Ítem Virtual Screening of Plant Volatile Compounds Reveals a High Affinity of Hylamorpha elegans (Coleoptera: Scarabaeidae) Odorant-Binding Proteins for Sesquiterpenes From Its Native Host(Oxford Univ Press, 2016) González-González, Angélica; Palma-Millanao, Rubén; Yáñez, Osvaldo; Rojas, Maximiliano; Mutis, Ana; Venthur, Herbert; Quiroz, Andrés; Ramírez, Claudio C.Hylamorpha elegans (Burmeister) is a native Chilean scarab beetle considered to be a relevant agricultural pest to pasture and cereal and small fruit crops. Because of their cryptic habits, control with conventional methods is difficult; therefore, alternative and environmentally friendly control strategies are highly desirable. The study of proteins that participate in the recognition of odorants, such as odorant-binding proteins (OBPs), offers interesting opportunities to identify new compounds with the potential to modify pest behavior and computational screening of compounds, which is commonly used in drug discovery, may help to accelerate the discovery of new semiochemicals. Here, we report the discovery of four OBPs in H. elegans as well as six new volatiles released by its native host Nothofagus obliqua (Mirbel). Molecular docking performed between OBPs and new and previously reported volatiles from N. obliqua revealed the best binding energy values for sesquiterpenic compounds. Despite remarkable divergence at the amino acid level, three of the four OBPs evaluated exhibited the best interaction energy for the same ligands. Molecular dynamics investigation reinforced the importance of sesquiterpenes, showing that hydrophobic residues of the OBPs interacted most frequently with the tested ligands, and binding free energy calculations demonstrated van der Waals and hydrophobic interactions to be the most important. Altogether, the results suggest that sesquiterpenes are interesting candidates for in vitro and in vivo assays to assess their potential application in pest management strategies.