Synthesis, chemical characterization, computational studies and biological activity of new DNA methyltransferases (DNMTs) specific inhibitor. Epigenetic regulation as a new and potential approach to cancer therapy.

This work deals with the synthesis, the chemical characterization of dibutyltin(IV) complex of caffeic acid (Bu2Sn(IV)HCAF, caf1) and its cytotoxic action on tumor cells. The coordination environment at the tin center was investigated by FTIR, (119)Sn{(1)H} cross polarization magic angle spinning, electrospray ionization mass spectroscopy in the solid state and UV-vis, fluorescence and (1)H, (13)C and (119)Sn NMR spectroscopy in solution phases. Density functional theory study confirmed the proposed structures in solution phase and indicated the most probably stable conformation. The effects on viability of breast cancer MDA-MB231, colorectal cancer HCT116, hepatocellular carcinoma HepG2 and Chang liver cells, an immortalized non-tumor hepatic cell line, have been investigated. The effect of a variation in structure of caf1 was found to lead to a change in the respective antiproliferative properties: caf1 induces loss of viability in HCT116, MDA-MB-231, and HepG2; the complex shows only moderate effects in non-tumor Chang liver cells. caf1 exerts lower cytotoxic activity than Bu2SnCl2, suggesting that the binding with H3CAF modulates the marked cytotoxic activity exerted by Bu2SnCl2; caf1 displays a considerably more pronounced antitumoural effect towards cell lines than caffeic acid. It is known that caffeic acid can modulate DNA (cytosine-5)-methyltransferases 1 (DNMT1) mediated DNA methylation. In this paper we demonstrate that caf1 treatment was able to induce a time-dependent reduction of global DNA methylated status. This effect was also confirmed by a concomitant reduction DNMT1 expression level. The effect induced by caf1 was more evident not only with respect to untreated cells but also compared to H3CAF treated cells.

Tomografía axial computarizada facial

Varón de 35 años de edad con antecedentes personales de rinitis sin predominio estacional, poliposis nasal, fumador de 2 paquetes al día, trabajador en tienda de calzado. Consulta hace 2 meses por rinorrea purulenta por fosa nasal derecha, tumefacción maxilar y epífora. Se realizó radiografía simple evidenciándose ocupación del seno maxilar derecho, sin nivel hidroaéreo. Se trató como una sinusitis aguda con antibioterapia durante 10 días; así la rinorrea mejoró pero persistió la epífora, la hipoestesia y la algia periorbitaria. Se remitió a otorrinolaringología donde se realizó endoscopia nasal observándose pólipos nasales. Ante la imposibilidad de completar el estudio por vía endoscópica, se solicitó una tomografía axial computarizada (TAC) de cráneo, que mostró una masa de partes blandas heterodensa que ocupaba la totalidad de la cavidad nasal, el seno maxilar derecho, y las celdillas etomoidales, con destrucción de paredes óseas (orbitaria inferior, superior y media de seno maxilar derecho).Se evidenció una imagen polipoidea y un nivel hidroaéreo en el seno maxilar izquierdo. El estudio anatomopatológico fue compatible con un papiloma invertido (AU)