, Volume 29, Issue 3, pp 515–526 | Cite as

Metal complexes of 3-(4-bromophenyl)-1-pyridin-2-ylprop-2-en-1-one thiosemicarbazone: cytotoxic activity and investigation on the mode of action of the gold(III) complex

  • Luciana B. P. Sâmia
  • Gabrieli L. Parrilha
  • Jeferson G. Da Silva
  • Jonas P. Ramos
  • Elaine M. Souza-Fagundes
  • Silvia Castelli
  • Venn Vutey
  • Alessandro Desideri
  • Heloisa Beraldo


Complexes [Au(PyCT4BrPh)Cl]Cl (1), [Pt(PyCT4BrPh)Cl]0.5KCl (2), and [Pd(PyCT4BrPh)Cl]KCl (3) were obtained with 3-(4-bromophenyl)-1-pyridin-2-ylprop-2-en-1-one thiosemicarbazone (HPyCT4BrPh). Although complexes (2) and (3) did not exhibit potent cytotoxic activity, HPyCT4BrPh and its gold(III) complex (1) proved to be highly cytotoxic against HL-60 (human promyelocytic leukemia) and THP-1 (human monocytic leukemia) cells, and against MDA-MB 231 and MCF-7 (human breast adenocarcinoma) solid tumor cells. Except for HL-60 cells, upon coordination to gold(III) a 2- to 3-fold increase in the cytotoxic effect was observed. An investigation on the possible biological targets of the gold(III) complex was carried out. Complex (1) but not the free thiosemicarbazone inhibits the enzymatic activity of thioredoxin reductase (TrxR). The affinity of 1 for TrxR suggests metal binding to a selenol residue in the active site of the enzyme. While HPyCT4BrPh was inactive, 1 was able to inhibit topoisomerase IB (Topo IB) activity. Hence, inhibition of TrxR and Topo IB could contribute to the mechanism of cytotoxic action of complex (1).

Graphical Abstract


Chalcone Thiosemicarbazone Metal complexes Cytotoxic activities Thioredoxin reductase Topoisomerase IB 


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Luciana B. P. Sâmia
    • 1
  • Gabrieli L. Parrilha
    • 1
  • Jeferson G. Da Silva
    • 2
  • Jonas P. Ramos
    • 3
  • Elaine M. Souza-Fagundes
    • 3
  • Silvia Castelli
    • 4
  • Venn Vutey
    • 4
  • Alessandro Desideri
    • 4
  • Heloisa Beraldo
    • 1
  1. 1.Departamento de QuímicaUniversidade Federal de Minas GeraisBelo HorizonteBrazil
  2. 2.Departamento de FarmáciaUniversidade Federal de Juiz de Fora (UFJF)Governador ValadaresBrazil
  3. 3.Departamento de Fisiologia e BiofísicaUniversidade Federal de Minas GeraisBelo HorizonteBrazil
  4. 4.Department of BiologyUniversity of Rome “Tor Vergata”RomeItaly

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