Table 2.

The TOP1 and TDP1 Inhibitory Potency, and Cytotoxicity of 33–45.

					GI50 ± SD (μM)[c]
Cpd	n	R	TOP1 Inhibition[a]	IC50 (μM) for TDP1[b]	HCT-116	MCF-7
4	/d	/	0/+	>111	75 ± 4.4	>100
33	0	H	+	>111	>100	>100
34	2	NMe2	+	37–111	11 ± 0.48	27 ± 1.5
35	3		0	18 ± 6.9	0.55 ± 0.17	1.2 ± 0.10
36	2	NEt2	0	>111	2.1 ± 0.23	1.6 ± 0.17
37	3		+	15 ± 2.4	2.4 ± 0.11	2.0 ± 0.10
38	2		+++	37–111	0.25 ± 0.02	6.4 ± 1.0
39	3		+	15 ± 2.8	1.3 ± 0.21	1.4 ± 0.13
40	2		++	>111	15 ± 1.08	18 ± 0.67
41	3		+	>111	3.3 ± 0.73	7.9 ± 1.0
42	3	OH	+	>111	38 ± 2.31	51 ± 1.6
43	3	NH(CH2)2OH	+	10 ± 3.8	0.29 ± 0.19	2.2 ± 1.2
44	3		0/+	>111	10 ± 1.2	7.0 ± 0.55
45	3		0	>111	>100	85 ± 3.8

^[a]TOP1 cleavage inhibitory activity of the compounds was semiquantitatively expressed relative to CPT at 1 μM as follows: 0, no inhibition; 0/+, less than 20%; +, between 20% and 50% activity; ++, between 50% and 75% activity; +++, between 75% and 95% activity.

^[b]IC₅₀ values for TDP1 inhibition, defined as the concentration of compound that inhibits 50% of enzyme activity, were detected through the gel-based assays.

^[c]The cytotoxicity GI₅₀ value was defined as the concentration corresponding to 50% cell growth inhibition and obtained from MTT assay. Every experiment was repeated at least three times independently.

^[d]“/” means “inapplicable”.