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. Author manuscript; available in PMC: 2017 Apr 28.
Published in final edited form as: J Med Chem. 2016 Apr 12;59(8):3840–3853. doi: 10.1021/acs.jmedchem.6b00003

Figure 1.

Figure 1

Representative Top1-mediated DNA cleavage assays. Two independent experiments are shown for the indicated compounds at the indicated concentrations. A. Concentration-response for 49 and 51. B. Comparison of four selected compounds 48–51 (the gel was cropped to only show the selected concentrations). The numbers and arrows at the left indicate cleavage site positions (see Experimental Section). Gel-based assays include positive controls (i.e., 1 and 6). The combined intensities of the bands observed at different drug concentrations in the DNA cleavage electrophoresis gels are used to estimate the abilities of the topoisomerase I poisons to stabilize the cleavage complexes through inhibition of the religation reaction at several different DNA cleavage sites. The “+”-based scoring system is based on the activity of 1 μM camptothecin (1): 0, no activity; +, between 20 and 50% activity; ++, between 50 and 75% activity at the most effective drug concentration.