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In vivo investigations into the carbene gold anticancer drug candidates NHC*-Au-SCN and NHC*-Au-Scyclo
Date Issued
2018-09-12
Date Available
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.
Sponsorship
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
Language
English
Status of Item
Peer reviewed
This item is made available under a Creative Commons License
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