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Arene–Ru II Complexes of Curcumin Exert Antitumor Activity via Proteasome Inhibition and Apoptosis Induction
Author(s) -
Bonfili Laura,
Pettinari Riccardo,
Cuccioloni Massimiliano,
Cecarini Valentina,
Mozzicafreddo Matteo,
Angeletti Mauro,
Lupidi Giulio,
Marchetti Fabio,
Pettinari Claudio,
Eleuteri Anna Maria
Publication year - 2012
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201200341
Subject(s) - curcumin , ruthenium , chemistry , proteasome , apoptosis , cancer cell , stereochemistry , biochemistry , cancer , biology , catalysis , genetics
Organometallic ruthenium(II) complexes of general formula [(η 6 ‐arene)Ru(curcuminato)Cl], with arene being p ‐ i PrC 6 H 4 Me ( 1 ), C 6 H 6 ( 2 ), and C 6 Me 6 ( 3 ), were synthesized, characterized, and evaluated for their antitumor effects. Specifically, we explored their ability to regulate the proteasome, a validated pharmacological target in cancer treatment. Ruthenium complexes inhibited isolated proteasomes to various extents, with the biological activity of these complexes depending on the nature of the bound arene; in particular, [(η 6 ‐arene)Ru(curcuminato)Cl] 2 suppressed proteasomal activities more potently than 1 , 3 , or free curcumin. Each complex also inhibited proteasomes in cultured colon cancer cells and consequently triggered apoptosis, with the [(η 6 ‐benzene)Ru(curcuminato)Cl] complex 2 being the most active. The influence on the oxidative status of HCT116 cells and the DNA binding ability of the [(η 6 ‐arene)Ru(curcuminato)Cl] complexes were studied. Complex 2 showed the highest antioxidant capacity; moreover, complexes 1 and 2 were shown to bind isolated DNA with higher affinity (up to threefold) than free curcumin. Collectively, our results demonstrate that the complexation of curcumin with ruthenium(II) is a promising starting point for the development of curcumin‐based anticancer drugs.