Add time:07/29/2019         Source:sciencedirect.com

As a further extension of our research work focusing on the development of gold(III)-dithiocarbamato derivatives as potential anticancer agents, the new complexes [AuIIIX2(dtc-Sar-O(t-Bu))] (X = Cl (1)/Br (2)) are here reported. The compounds were characterized by means of FT-IR, ESI mass, and mono- and multidimensional NMR spectroscopy. In order to get further insights into the possible behavior under physiological conditions, their affinity toward selected model biomolecules was spectroscopically investigated in detail. In this regard, they seem to react very slowly with isolated dAMP (but not dGMP), forming a species identified as [AuIII(dtc-Sar-O(t-Bu))(dAMP-N1,C6NH)]+. In presence of GSH they undergo sudden reduction to the gold(I) counterpart [AuIII2(dtc-Sar-O(t-Bu))2], whereas only secondary interactions seem to occur when reacted with BSA. According to in vitro cytotoxicity studies, both complexes turned out to be highly effective toward all the human tumor cell lines evaluated (HeLa, L540 and U937), reporting IC50 values lower than cisplatin. Apoptosis was proved a major cell death mechanism and, accordingly, DNA fragmentation was observed. Remarkably, cell cycle progression was negligibly affected, thus supporting the hypothesis of a different mechanism of action from clinically-established platinum-based drugs.

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