Comprehensive analysis of crystal structure, spectroscopic properties, quantum chemical insights, and molecular docking studies of two pyrazolopyridine compounds: potential anticancer agents.

Autor: Polo-Cuadrado E; Laboratorio Síntesis Orgánica y Actividad Biológica (LSO-Act-Bio), Instituto de Química de Recursos Naturales, Universidad de Talca Casilla 747 Talca 3460000 Chile mgutierrez@utalca.cl., López-Cuellar L; Laboratorio Síntesis Orgánica y Actividad Biológica (LSO-Act-Bio), Instituto de Química de Recursos Naturales, Universidad de Talca Casilla 747 Talca 3460000 Chile mgutierrez@utalca.cl.; Universidad de la Amazonia, Programa de Química Cl. 17 Diagonal 17 con, Cra. 3F Florencia 180001 Colombia., Acosta-Quiroga K; Doctorado en Química, Departamento de Química Inorgánica y Analítica, Universidad de Chile Santiago Chile., Rojas-Peña C; Doctorado en Química, Departamento de Química Inorgánica y Analítica, Universidad de Chile Santiago Chile., Brito I; Departamento de Química, Facultad de Ciencias Básicas, Universidad de Antofagasta Avenida. Universidad de Antofagasta, Campus Coloso Antofagasta 02800 Chile., Cisterna J; Departamento de Química, Facultad de Ciencias, Universidad Católica del Norte Sede Casa Central, Av. Angamos 0610 Antofagasta Chile., Trilleras J; Grupo de Investigación en Compuestos Heterocíclicos, Universidad del Atlántico Puerto Colombia 081007 Colombia., Alderete JB; Instituto de Química de Recursos Naturales (IQRN), Universidad de Talca Avenida Lircay S/N, Casilla 747 Talca Chile., Duarte Y; Center for Bioinformatics and Integrative Biology, Facultad de Ciencias de la Vida, Universidad, Andrés Bello Av. Republica 330 Santiago 8370146 Chile yorley.duarte@unab.cl.; Interdisciplinary Centre for Neuroscience of Valparaíso, Facultad de Ciencias, Universidad de Valparaíso Valparaíso 2381850 Chile., Gutiérrez M; Laboratorio Síntesis Orgánica y Actividad Biológica (LSO-Act-Bio), Instituto de Química de Recursos Naturales, Universidad de Talca Casilla 747 Talca 3460000 Chile mgutierrez@utalca.cl.
Jazyk: angličtina
Zdroj: RSC advances [RSC Adv] 2023 Oct 16; Vol. 13 (43), pp. 30118-30128. Date of Electronic Publication: 2023 Oct 16 (Print Publication: 2023).
DOI: 10.1039/d3ra04874h
Abstrakt: In this study, two pyrazolo[3,4- b ]pyridine derivatives (4a and 4b) were grown using a slow evaporation solution growth technique and characterized by FT-IR, HRMS, 1 H/ 13 C NMR spectroscopy, and X-ray crystallography. The 4a and 4b structures crystallized in monoclinic and triclinic systems with space groups P 2 1 / n and P 1̄, respectively. Theoretical calculations were performed at the DFT/B3LYP level for the optimized geometries. The results were in excellent agreement with the experimental data (spectroscopic and XRD). This investigation encompasses molecular modeling studies including Hirshfeld surface analysis, energy framework calculations, and frontier molecular orbital analysis. Intermolecular interactions within the crystal structures of the compounds were explored through Hirshfeld surface analysis, which revealed the notable presence of hydrogen bonding and hydrophobic interactions. This insight provides valuable information on the structural stability and potential solubility characteristics of these compounds. The research was extended to docking analysis with eight distinct kinases (BRAF, HER2, CSF1R, MEK2, PDGFRA, JAK, AKT1, and AKT2). The results of this analysis demonstrate that both 4a and 4b interact effectively with the kinase-binding sites through a combination of hydrophobic interactions and hydrogen bonding. Compound 4a had the best affinity for proteins; this is related to the fact that the compound is not rigid and has a small size, allowing it to sit well at any binding site. This study contributes to the advancement of kinase inhibitor research and offers potential avenues for the development of new therapeutic agents for cancer treatment.
Competing Interests: There are no conflicts to declare.
(This journal is © The Royal Society of Chemistry.)
Databáze: MEDLINE
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