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

Cristina Prinzivalli, Michela Giuliano, Lorenzo Pellerito, Tiziana Fiore, Michelangelo Scopelliti, Girolamo Casella, Claudia Pellerito, Ornella Pellerito, Giulia Grasso, Cristina Prinzivalli, Claudia Pellerito, Michelangelo Scopelliti, Piera Sabatino, Tiziana Fiore, Lorenzo Pellerito, Michela Giuliano, Elisabetta Foresti, Girolamo Casella, Michele Abbate, Ornella Pellerito

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7 Citations (Scopus)

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 aconsequence of a long range O · · · Sn interaction. Crystallographic and NMR findings confirm this situationboth in solid state and solution. Biological finding evidenced a clear cytotoxic action of the complexes in hepatocellularcarcinoma cell cultures: one of the complexes induced an 80% cell viability reduction after 24 htreatment in HepG2 cells. This effect was accompanied by the appearance of biochemical signs of apoptosis. InChang liver cells, the same compound induced only modest effects, suggesting a potential use as anti-cancerdrug. Preliminary evaluations on hyperacetylation state of histone H3 in tributyltin-valproate treated HepG2cells showed an increase in Ac-H3 (histone H3 acetylated at lys-9 and lys-14), suggesting that the compoundmaintains the deacetylation inhibition activity of its ligand valproate.
Original languageEnglish
Pages (from-to)16-25
Number of pages10
JournalJournal of Inorganic Biochemistry
Volume125
Publication statusPublished - 2013

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Inorganic Chemistry

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    Prinzivalli, C., Giuliano, M., Pellerito, L., Fiore, T., Scopelliti, M., Casella, G., Pellerito, C., Pellerito, O., Grasso, G., Prinzivalli, C., Pellerito, C., Scopelliti, M., Sabatino, P., Fiore, T., Pellerito, L., Giuliano, M., Foresti, E., Casella, G., Abbate, M., & Pellerito, O. (2013). Synthesis, chemical characterization and biological activity of newhistone acetylation/deacetylation specific inhibitors: A novel andpotential approach to cancer therapy. Journal of Inorganic Biochemistry, 125, 16-25.