Table 1.

Tdp1 and Top1 Inhibitory Activity

Compd	Tdp1	Top1	Compd	Tdp1a	Top1b
1	++	+++	40	++(+)	++(+)
2	+++	NT	41	0	0
9	0	0	42	0	0
10	0	0	43	+++	0
11	0	(+)	49	0	+++
12	0	+	50	0	+
13	0	0	51	++	++
14	+	++	52	(+)	+++
15	0	+(+)	53	0	++
18	0	0	54	+++	++++
19	0	0	55	+++	++++
20	0	0	56	0	++
22	+(+)	0	57	++	0
23	++(+)	++(+)	58	0	+
24	+	(+)	59	+	+(+)
25	+	0	60	+(+)	++(+)
26	+	(+)	61	0	0
29	+	(+)	62	++(+)	++(+)
30	0	0	63	0	++
31	+	(+)	72	0	++
32	0	+	73	0	++
33	0	+	74	++	+++
34	0	+	77	0	++(+)
35	0	0	84	+++	+(+)
36	0	+	85	+(+)	+++
38	0	0	89	+++	++(+)

^aTdp1 IC₅₀ was determined by duplicate using a semiquantitative scale: 0, IC₅₀ > 111 μM; +, IC₅₀ between 37–111 μM; ++, IC₅₀ between 12–37 μM; +++, IC₅₀ between 1–12 μM, ++++, IC₅₀ < 1 μM. Active compounds were further evaluated for a more accurate value.

^bCompound-induced DNA cleavage due to Top1 inhibition is graded by the following semiquantitative scale relative to 1 μM camptothecin (90) or MJ-III-65 (91): 0, no detectable activity; +, weak activity; ++, similar activity to compound 91; +++, greater activity than 91; ++++, equipotent to 90. The (+) ranking indicates the activity lies between two given values.

NT: not tested.