Table 1.

The TOP1 and TDP1 Inhibitory Potency, and Cytotoxicity of 10-23.

					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
10	0	Ac	+	>111	>100	>100
11	0	H	0	>111	>100	>100
12	2	NHMe	+++	>111	1.3 ± 0.12	2.2 ± 0.06
13	3		+	>111	12 ± 1.2	33 ± 5.0
14	2	NMe2	+	37–111	4.6 ± 0.41	8.5 ± 0.91
15	3		+	>111	36 ± 1.3	54 ± 4.9
16	2		+	>111	>100	22 ± 7.7
17	3		++	>111	1.8 ± 0.32	6.6 ± 1.3
18	2		+	37–111	7.7 ± 0.56	7.0 ± 1.3
19	3		++	>111	1.5 ± 0.21	0.93 ± 0.07
20	2		++	>111	2.9 ± 0.45	2.7 ± 0.23
21	3		0	>111	16 ± 3.6	64 ± 3.9
22	2	NH(CH2)2NMe2	+	>111	9.1 ± 1.0	9.1 ± 2.4
23	1	COOEt	0	>111	>100	91 ± 5.9

^[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”.