The anticancer drug candidate 1,3-dibenzyl-4,5-diphenyl-imidazol-2-ylidene gold(I) thiocyanate (NHC*-Au-SCN) and its cyclohexane thiolate derivative (NHC*-Au-Scyclo) exhibited very good activity against human colon cancer with GI50 values against human HCT116 colon cancer cells of 0.40 and 1.65 μM, respectively. In addition, inhibition of the mammalian thioredoxin reductase (TrxR) was observed with IC50 values of 0.77 ± 0.34 µM for NHC*-Au-SCN and 13 ± 4 µM for NHC*-Au-Scyclo. This encouraged maximum tolerable dose (MTD) experiments in mice, where MTD values of 10 mg/kg for NHC*-Au-SCN and 30 mg/kg for NHC*-Au-Scyclo were determined with single injections to groups of 2 mice. In the subsequent tumor xenograft experiment NHC*-Au-SCN and NHC*-Au-Scyclo were applied three times at two doses in groups of 6 HCT116 tumor-bearing NMRI:nu/nu mice. The control group comprising 6 mice was treated with the solvent only. NHC*-Au-SCN at the dose of 5 and 10 mg/kg and NHC*-Au-Scyclo at the higher dose of 15 and 30 mg/kg showed tolerability towards the drugs, while no significant body weight loss was seen in both groups. NHC*-Au-SCN exerted only weak antitumoral activity reflected by T/C values of 0.81 and 0.65. The tumor volume growth reduction induced by NHC*-Au-Scyclo was better, with optimal T/C values of 0.58 and 0.31 being observed at doses of 15 mg/kg and 30 mg/kg, respectively. Alterations in dosing and/or application schedules might further improve the antitumoral activity, particularly for NHC*-Au-Scyclo.
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