Evaluation of doxorubicin and β-lapachone analogs as anticancer agents, a biological and computational study Itzel Mercado‐Sánchez, Julio López, Rogelio Chávez‐Rocha, Ismael Vargas‐Rodríguez, Adán Bazán‐Jiménez, et al. Chemical Biology and Drug Design, 2024 We have conducted an experimental and computational evaluation of new doxorubicin (4a–c) and β‐lapachone (5a–c) analogs. These novel anticancer analogs were previously synthesized, but had not been tested or characterized until now. We have evaluated their antiproliferative and DNA cleavage inhibition properties using breast (MCF‐7 and MDA‐MB‐231) and prostate (PC3) cancer cell lines. Additionally, cell cycle analysis was performed using flow cytometry. Computational studies, including molecular docking, pharmacokinetic properties, and an analysis of DFT and QTAIM chemical descriptors, were performed to gain insights into the electronic structure and elucidate the molecular binding of the new β‐lapachone and doxorubicin analogs with a DNA sequence and Topoisomerase II (Topo II)α. Our results show that 4a analog displays the highest antiproliferative activity in cancer cell lines by inducing cell death. We observed that stacking interactions and hydrogen bonding are essential to stabilize the molecule‐DNA‐Topo IIα complex. Moreover, 4a and 5a analogs inhibited Topo's DNA cleavage activity. Pharmacodynamic results indicated that studied molecules have favorable adsorption and permeability properties. The calculated chemical descriptors indicate that electron accumulation in quinone rings is relevant to the reactivity and biological activity. Based on our results, 4a is a strong candidate for becoming an anticancer drug.
Modeling Adsorption of CO2 in Rutile Metallic Oxide Surfaces: Implications in CO2 Catalysis Rogelio Chávez-Rocha, Itzel Mercado-Sánchez, Ismael Vargas-Rodriguez, Joseelyne Hernández-Lima, Adán Bazán-Jiménez, et al. Molecules, 2023 CO2 is the most abundant greenhouse gas, and for this reason, it is the main target for finding solutions to climatic change. A strategy of environmental remediation is the transformation of CO2 to an aggregated value product to generate a carbon-neutral cycle. CO2 reduction is a great challenge because of the large C=O dissociation energy, ~179 kcal/mol. Heterogeneous photocatalysis is a strategy to address this issue, where the adsorption process is the fundamental step. The focus of this work is the role of adsorption in CO2 reduction by means of modeling the CO2 adsorption in rutile metallic oxides (TiO2, GeO2, SnO2, IrO2 and PbO2) using Density Functional Theory (DFT) and periodic DFT methods. The comparison of adsorption on different metal oxides forming the same type of crystal structure allowed us to observe the influence of the metal in the adsorption process. In the same way, we performed a comparison of the adsorption capability between two different surface planes, (001) and (110). Two CO2 configurations were observed, linear and folded: the folded conformations were observed in TiO2, GeO2 and SnO2, while the linear conformations were present in IrO2 and PbO2. The largest adsorption efficiency was displayed by the (001) surface planes. The CO2 linear and folded configurations were related to the interaction of the oxygen on the metallic surface with the adsorbate carbon, and the linear conformations were associated with the physisorption and folded configurations with chemisorption. TiO2 was the material with the best performance for CO2 interactions during the adsorption.
Grammatical evolution-based design of SARS-CoV-2 main protease inhibitors Francisco Frausto-Parada, Ismael Várgas-Rodríguez, Itzel Mercado-Sánchez, Adán Bazán-Jiménez, Erik Díaz-Cervantes, et al. Physical Chemistry Chemical Physics, 2022 A series of SARS-CoV-2 main protease (SARS-CoV-2-Mpro) inhibitors were modeled using evolutive grammar algorithms.
Modeling adsorption and optical properties for the design of co2 photocatalytic metal-organic frameworks Priscila Chacón, Joseelyne G. Hernández-Lima, Adán Bazán-Jiménez, Marco A. García-Revilla Molecules, 2021 Four Metal-Organic Frameworks (MOFs) were modeled (IRMOF-C-BF2, IRMOF-C-(2)-BF2, IRMOF-C’-BF2, and IRMOF-C-CH2BF2) based on IRMOF-1. A series of linkers, based on Frustrated Lewis Pairs and coumarin moieties, were attached to IRMOF-1 to obtain MOFs with photocatalytic properties. Four different linkers were used: (a) a BF2 attached to a coumarin moiety at position 3, (b) two BF2 attached to a coumarin moiety in positions 3 and 7, (c) a BF2 attached in the coumarin moiety at position 7, and (d) a CH2BF2 attached at position 3. An analysis of the adsorption properties of H2, CO2, H2O and possible CO2 photocatalytic capabilities was performed by means of computational modeling using Density Functional Theory (DFT), Time-Dependent Density Functional (TD-DFT) methods, and periodic quantum chemical wave function approach. The results show that the proposed linkers are good enough to improve the CO2 adsorption, to hold better bulk properties, and obtain satisfactory optical properties in comparison with IRMOF-1 by itself.
