In vivo investigations into the carbene gold anticancer drug candidates NHC*-Au-SCN and NHC*-Au-Scyclo

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Title: In vivo investigations into the carbene gold anticancer drug candidates NHC*-Au-SCN and NHC*-Au-Scyclo
Authors: Walther, Wolfgang
Dada, Oyinlola
Ott, Ingo
Prochnicka, Agnieszka
Büttner, Britta
Zhu, Xiangming
Tacke, Matthias
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Date: 12-Sep-2018
Online since: 2019-05-16T11:13:34Z
Abstract: 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.
Funding Details: University College Dublin
Type of material: Journal Article
Publisher: Research Trends
Journal: Trends in Cancer Research
Volume: 13
Start page: 63
End page: 70
Copyright (published version): 2018 Research Trends
Keywords: Carbene-gold anticancer drugNCI 60 cancer cell panelThioredoxin reductaseHCT116 colon cancerXenograft mouse model
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Language: en
Status of Item: Peer reviewed
Appears in Collections:Chemistry Research Collection

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