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GIROLAMO CASELLA

Synthesis, chemical characterization and biological activity of new histone acetylation/deacetylation specific inhibitors: A novel and potential approach to cancer therapy.

  • Autori: Pellerito, O; Prinzivalli, C; Foresti, E; Sabatino, P; Abbate, M; Casella, G; Fiore, T; Scopelliti, M; Pellerito, C; Giuliano, M; Grasso, G; Pellerito, L
  • Anno di pubblicazione: 2013
  • Tipologia: Articolo in rivista (Articolo in rivista)
  • OA Link: http://hdl.handle.net/10447/73018

Abstract

Three new triorganotin(IV) complexes of valproic acid (vp1, Me3Sn-valproate; vp2, Bu3Sn-valproate; vp3, Ph3Sn-valproate) have been synthesized and investigated by spectroscopic and biological methods. An anionic, monodentate valproate ligand was observed, ester-like coordinating the tin atom on a tetracoordinated, monomeric environment. The structures, though, can distort towards a penta-coordination, as a consequence of a long range O · · · Sn interaction. Crystallographic and NMR findings confirm this situation both in solid state and solution. Biological finding evidenced a clear cytotoxic action of the complexes in hepatocellular carcinoma cell cultures: one of the complexes induced an 80% cell viability reduction after 24 h treatment in HepG2 cells. This effect was accompanied by the appearance of biochemical signs of apoptosis. In Chang liver cells, the same compound induced only modest effects, suggesting a potential use as anti-cancer drug. Preliminary evaluations on hyperacetylation state of histone H3 in tributyltin-valproate treated HepG2 cells showed an increase in Ac-H3 (histone H3 acetylated at lys-9 and lys-14), suggesting that the compound maintains the deacetylation inhibition activity of its ligand valproate.