Abstract
In the last few years gold(III) complexes have attracted growing attention in the medicinal chemistry community as candidate anticancer agents. In particular some organogold(III) compounds manifested quite attractive pharmacological behaviors in preclinical studies. Here we compare the chemical and biological properties of the novel organogold(III) complex [Au(bipydmb−H)(NH(CO)CH3)][PF6] (Aubipyaa) with those of its parent compounds [Au(bipydmb−H)(OH)][PF6] (Aubipyc) and [Au2(bipydmb−H)2)(μ−O)][PF6]2 (Au2bipyc), previously synthesized and characterized. The three study compounds were comparatively assessed for their antiproliferative actions against HCT-116 cancer cells, revealing moderate cytotoxic effects. Proapoptotic and cell cycle effects were also monitored. Afterward, to gain additional mechanistic insight, the three gold compounds were challenged against the model proteins HEWL, RNase A and cytochrome c and reactions investigated through UV–Vis and ESI–MS analysis. A peculiar and roughly invariant protein metalation profile emerges in the three cases consisting of protein binding of {Au(bipydmb−H)} moieties. The implications of these results are discussed in the frame of current knowledge on anticancer gold compounds.
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Acknowledgments
This work was supported by Beneficentia Stiftung (Vaduz, Liechtenstein), Ente Cassa di Risparmio di Firenze and AIRC (IG-16049). MAC gratefully acknowledges the Regione Autonoma della Sardegna for funds financed on L.R. 7/2007 bando 2013. CIRCMSB and Cost Action CM1105 are gratefully acknowledged. The MetMed group and GB acknowledge the group of Prof. A. Arcangeli for the biological studies’ support. LM thanks C.A. Scuotto for the help during his traineeship.
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Massai, L., Cirri, D., Michelucci, E. et al. Organogold(III) compounds as experimental anticancer agents: chemical and biological profiles. Biometals 29, 863–872 (2016). https://doi.org/10.1007/s10534-016-9957-x
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DOI: https://doi.org/10.1007/s10534-016-9957-x