Narváez Pita, Xiomara

Profile Picture

Filters

2012 - 20202
Reset filters

Settings

Citations

Publication Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Publication
    Síntesis y estudios mecanísticos de complejos de molibdenoceno: Interacción de agentes metálicos anti-cáncer con el transporte de proteínas
    (2012) Narváez Pita, Xiomara; Meléndez, Enrique; College of Arts and Sciences - Sciences; Rivera, Nilka; Morell, Luis; Department of Chemistry; López, Ricardo R.
    Nuevos complejos organometálicos fueron sintetizados, partiendo del dicloruro de molibdenoceno (Cp2MoCl2) y cuatro ligandos: L-Acido ascórbico(L-AA), 6-o-palmitoil-L- acido ascórbico (PAA), Etil maltol y D-penicilamina, Los productos obtenidos fueron purificados y caracterizados por espectroscopía de resonancia magnética nuclear de protón (1H-NMR), infrarrojo (FT-IR), y análisis elemental, para elucidar su estructura. Estos complejos presentan estabilidad a pH fisiológico y tres de ellos son altamente solubles en agua, excepto el Cp2Mo(PAA), el cual es ligeramente soluble. La técnica de voltametría cíclica, (CV), se usó para determinar el comportamiento redox de los complejos sintetizados, en CH3CN mostrando comportamientos electroquímicos reversibles, y mayor estabilidad de estos complejos comparados con el compuesto de partida el dicloruro de molibdenoceno. Estudios similares se hicieron bajo condiciones fisiológicas, en amortiguador Tris-HCl a pH=7.4, donde el comportamiento redox de Cp2Mo(L-AA), Cp2Mo(PAA), y [Cp2Mo(etil maltol)]Cl, fue irreversible y para el complejo [Cp2Mo(D-penicilamina)]Cl fue reversible. Se estudio la interacción entre los complejos y la proteína Ubiquitina, por UV-VIS, voltametría cíclica (CV), fluorescencia, y dicroísmo circular(CD), encontrándose alguna clase de interacción. Las actividades citotóxicas de los complejos sintetizados, fueron investigadas en líneas celulares de cáncer de mama MCF-7 y de cáncer de colon HT-29 usando el ensayo MTT a 72 horas. El complejo Cp2Mo(PAA) mostró mayor actividad citotóxica con un valor del IC50 de 0.33 mM, seguido del Cp2Mo(L-AA) con un valor de 0.8 mM, el [Cp2Mo(etil maltol)]Cl con 1.60 mM, y el [Cp2Mo(D-penicilamina)]Cl con 1.78 mM. En cuanto a la línea celular de HT-29, el complejo de Cp2Mo(PAA) mostró un IC50 de 0.050 mM, siendo el más activo; seguido del Cp2Mo(L-AA), con un valor de IC50 de 0.55 mM y e[Cp2Mo(etil maltol)]Cl con 0.63mM. Incluir esta clase de ligandos en el dicloruro de molibdenoceno, mejoró sus propiedades antitumorales.
  • Thumbnail Image
    Publication
    Synthesis of novel ferrocene complexes with androgens vectors, biological activity and their interactions with proteins
    (2020-12-11) Narváez Pita, Xiomara; Meléndez, Enrique; College of Arts and Sciences - Sciences; Pastrana Ríos, Belinda; Ríos Steiner, Jorge; Ríos Guillet, Robert; Department of Chemistry; Giraldo Zapata, Martha C.
    Four novel complexes were synthetized by aldol condensation reaction and characterized by different spectroscopic techniques using ferrocenecarboxaldehyde as starting material, and using the hormones ( 3α-hydroxy androstan-17-one (cis-androsterone), 3β-hydroxyandrostan-17-one (trans-androsterone), 3β-hydroxy pregn-5-en-20-one (pregnenolone) and 3β-hydroxy dehydroandrostan-17-one (dehydroepiandrosterone, DHEA)) as pendants groups. Three of these complexes 16-ferrocenylidene-3α-hydroxy androstan-17-one, 16-ferrocenylidene-3β-hydroxy androstan-17-one, 21-ferrocenylidene-3β-hydroxy pregn-5-en-20-one were crystallized using vapor diffusion in a benzene/pentane system to study their structure by single crystal X-ray diffraction. The cytotoxic activity of the novel complexes on the hormone-dependent MCF-7 and -independent MDA-MB231 breast cancers and HT-29 colon cancer cell lines were evaluated through colorimetric MTT assay. The IC50 values obtained for the complexes were Fc-cis-androsterone [14 ±3 μM (MCF-7), 12.5±0.2 μM (MDA-MB231), 1.2±0.4 μM (HT-29)]; Fc-trans-androsterone [20±1 μM (MCF-7), 26±0.5 μM (MDA-MB231),18±0.3 μM (HT-29)]; Fc-DHEA [27±2 μM (MCF-7), 21±0.6 μM (MDA-MB231), 33.1±0.4 μM (HT-29)]; and Fc-pregnenolone [124±22 μM (MCF-7), 72±6 μM (MDA-MB231), 126±7 μM (HT-29)]. These species demonstrated that the synergism between the ferrocene and the steroid improves notably the antitumoral properties on the cell lines studied when compared with the starting material and the standards Tamoxifen [47 ±2 μM (MCF-7)], and cisplatin [66 ±2 μM (HT-29)]. Molecular modeling was performed to study the interaction of the novel complexes synthetized with Estrogen Receptor Alpha (ER-α) (PDB: 2YAT) using AUTODOCK VINA 4.1. The docking studies showed that all the complexes occupy the same binding site in the estrogen receptor. The results suggest that the protein-ligands interactions were mainly hydrophobic, showing that Fc-pregnenolone complex has the highest affinity constant to ER-α compared to the other complexes. Human Serum Albumin-ferrocene steroid conjugates interactions were studied using fluorescence quenching spectroscopy to understand the mechanism of action of the protein, in the transport of anticancer drugs; Ksv constants values showed the fluorescence quenching of HAS-ferrocene complexes are driven by a static mechanism and the thermodynamic parameters (ΔH and ΔS) that were obtained using Van’t Hoff plot indicated these interactions are mainly hydrophobic. Molecular modeling docking studies were performed using AUTODOCK Vina 4.1 program to corroborate the hydrophobic interactions of the novel complexes with the protein HSA (PDB: 1HA2) and Fc-pregnenolone complex showed the highest affinity to drug binding site II.