In Vitro and In Vivo Investigations into the Carbene Copper Bromide Anticancer Drug Candidate WBC4

Author(s): Wolfgang Walther, Iduna Fichtner, Frauke Hackenberg, Wojciech Streciwilk, Matthias Tacke

Journal Name: Letters in Drug Design & Discovery

Volume 11 , Issue 7 , 2014

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Graphical Abstract:


The anticancer drug candidate 1,3-di(p-methoxybenzyl)-4,5-di(p-isopropylphenyl)-imidazol-2-ylidene copper( I) bromide (WBC4) was tested on the NCI 60 cancer cell panel in vitro. WBC4 showed very good activity against a wide range of human cancer cell lines inclusive renal cell cancer with an average GI50 value of 288 nM. This encouraged maximum tolerable dose (MTD) experiments in mice, where a MTD value of 10 mg/kg was determined with single injections to groups of 2 mice. In the following tumor xenograft experiment WBC4 was given at 5 and 10 mg/kg in 5 injections to two cohorts of 6 CAKI-1 tumor-bearing NMRI:nu/nu mice, while a control cohort of 6 mice was treated with solvent only. At the higher dose of 10 mg/kg WBC4 showed borderline toxicity leading to 2 mortalities, while a significant T/C value of 0.38 was observed on day 32. At the lower dose of 5 mg/kg WBC4 induced mild and reversible body weight loss with no toxic deaths. At this dose WBC4 showed an identical significant T/C value of 0.38 on day 32, when compared to the treatment group. Immunohistochemistry for the proliferation marker Ki-67 did not show significant changes due to WBC4 treatment in the animals. However, anti-angiogenic effects by WBC4 treatment were observed in CD31 immunohistochemistry. Here, significant reduction in microvessel number, area and ratio was determined in tumors treated with 10 mg/kg of WBC4.

Keywords: Anticancer drug, Carbene-copper complex, NCI 60 cancer cell panel, CAKI-1 renal cell cancer, Xenograft mouse model.

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Article Details

Year: 2014
Page: [825 - 832]
Pages: 8
DOI: 10.2174/1570180811666140529004102
Price: $65

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