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. Author manuscript; available in PMC: 2020 Dec 8.
Published in final edited form as: J Med Chem. 2019 Nov 18;62(22):10182–10203. doi: 10.1021/acs.jmedchem.9b01065

Figure 3. Antitumor activity of prototypes 3 and 7.

Figure 3.

Compounds 7 (a) and 3 (b) demonstrate the ability to significantly inhibit TOP2A-dependent TCF-transcription using SW620 tumor organoids transduced with the TOPflash luminescent reporter. Compounds 7 (c) and 3 (d) also demonstrated the ability to reverse EMT using SW620 tumor organoids transduced with EcadPro-RFP or VimPro-GFP EMT biomarker reporters over a 72 h treatment time course as indicated. Reversion of EMT is characterized by downregulation of vimentin and upregulation of E-cadherin promoter activity. Representative tumor organoid images are shown above each bar graph. (e) Compounds 7 and 3 also significantly inhibit colony formation over seven days, which is a measure of the loss of cancer stem cell stemness. (f) SW620 tumor organoids were treated with 7 and 3 for 72 h, tumor organoids were dissociated, and viable cell invasive potential was measured for additional 72h incubation. Compounds 3 and 7 both significantly inhibit the invasive potential of SW620 cells. Significance was determined using the Student’s t-test analysis.