Organometallic ruthenium(II) complexes of general formula [(η6-arene)Ru(curcuminato)Cl], with arene being p-iPrC6H4Me (1), C6H6 (2), and C6Me6 (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, [(η6-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 [(η6-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 [(η6-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.

Arene-Ru(II) complexes of curcumin exert antitumor activity via proteasome inhibition and apoptosis induction

BONFILI, LAURA;PETTINARI, Riccardo;CUCCIOLONI, Massimiliano;CECARINI, Valentina;MOZZICAFREDDO, MATTEO;ANGELETTI, Mauro;LUPIDI, Giulio;MARCHETTI, Fabio;PETTINARI, Claudio;ELEUTERI, Anna Maria
2012-01-01

Abstract

Organometallic ruthenium(II) complexes of general formula [(η6-arene)Ru(curcuminato)Cl], with arene being p-iPrC6H4Me (1), C6H6 (2), and C6Me6 (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, [(η6-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 [(η6-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 [(η6-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.
2012
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11581/249367
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