Síntesis y caracterización de compuestos heterobimetálicos Cu/V con potencial actividad antineoplásica

• Autores: Beatriz Martínez Valencia
• Directores de la Tesis: Enrique González Vergara (dir. tes.), Francisco Javier Melendez Bustamante (codir. tes.)
• Lectura: En la Benemérita Universidad Autónoma de Puebla (BUAP) ( México ) en 2021
• Idioma: español
• Enlaces
  • Tesis en acceso abierto en: hdl.handle.net
• Resumen
  • español

    “El cáncer representa un importante problema de salud pública a nivel mundial. Si bien se están realizando avances significativos en diferentes frentes para combatir la enfermedad, el desarrollo de nuevos medicamentos a base de metales con capacidades citotóxicas es de gran relevancia.

    Durante la última década, los complejos de cobre y vanadio han mostrado propiedades prometedoras para el tratamiento de varios tipos de cáncer. En particular, las Casiopeinas®, son un grupo de complejos a base de cobre, que han recibido atención específica, y su mecanismo de acción ha sido ampliamente estudiado ya que su estructura es simple y su síntesis es muy asequible. En este proyecto de tesis dos nuevas moléculas fueron diseñadas para proporcionar cobre y vanadio, dos metales con capacidades anticancerígenas comprobadas en la misma estructura molecular. Aquí, se informan posibles profármacos que liberarían los dos metales en forma utilizable para actuar conjuntamente contra células cancerosas”.

  • English

    Cancer represents a major public health problem worldwide. While significant advances in different fronts are being made to combat the disease, the development of new metal-based drugs with cytotoxic capabilities is of high relevance. In particular, Casiopeinas®, a group of copper-based complexes, has received specific attention, and their mechanism of action has been extensively studied since their structure is simple and their synthesis is affordable. In this thesis project, two new molecules were designed to provide Cu and V in the same molecular structure, two metals with proven anticancer capabilities. Here, potential prodrugs that would release the two metals in usable form to act in conjunction against cancer cells are reported. Cyclo-tetravanadate ion bridges the new series of Casiopeina-like compounds with the formulas [Cu(Orn)(bipy)]-(V4O12)-[Cu(Orn)(bipy)], [Cu(Gly)(phen)(H20)]2 [Cu(Gly)(phen)]– (V10O28)-[Cu(Gly)(phen)] where bipy is 2,2´-bipyridine and phen is 1,10-phenantroline. The compounds were synthesized and characterized by different techniques: elemental analysis, UV-Vis, FTIR, Raman and EPR spectroscopies, 51V nuclear magnetic resonance, cyclic voltammetry, thermogravimetric analysis, and single-crystal X-ray diffraction. The molecular structures and the spectroscopic and electronic properties of the studied compounds were calculated through the Density Functional Theory (DFT). Optimized structures, theoretical IR, and Raman spectra were obtained. Docking analysis was also performed to examine DNA interactions with the casiopeina-like complexes. Interactions with DNA are composed of πinteractions, hydrophobic interactions, hydrogen bonds, and saline bridge. In the case of the compound containing ornithine, the hydrogen bonds and saline bridge serve as an anchor to raise the interaction energy, which contrasts with the glycine-containing compound that is equivalent to Cassiopeina® VII-gly, whose interaction energy is similar to Cassiopeina® II-Gly, which is in phase I of clinical trials in Mexico. For RNA, the interactions are dominated by hydrogen bonds and saline bridge. Only very weak hydrophobic interactions are present. The interaction energies of the compounds here reported are comparable with other copper complexes that have demonstrated high antitumor activity in vitro as well as in vivo.

    Compounds after dissociation provide two metals that can interact with important biological targets in a variety of cancer cell models.