. Author manuscript; available in PMC: 2008 Aug 28.

Published in final edited form as: J Med Chem. 2006 Oct 19;49(21):6283–6289. doi: 10.1021/jm060564z

Table 1.

Cytotoxicities and Topoisomerase I Inhibitory Activities of Indenoisoquinoline Analogues.

	cytotoxicity (GI50 in μM)^a
compd	lung HOP-62	colon HCT-116	CNS SF-539	melanoma UACC-62	ovarian OVCAR-3	renal SN12C	prostate DU-145	breast MDA-MB-435	MGM^b	Top 1 Cleavage^c
1	1.30	35.0	41.0	4.20	73.0	68.0	37.0	96.0	20.0	++
2	0.06	0.13	0.26	0.25	0.31	0.31	0.04	1.21	0.16 ± 0.02	+++
6	<0.010	<0.010	0.037	<0.010	0.085	<0.010	<0.010	0.020	0.079 ± 0.023	++++
7	0.447	1.99	0.398	0.269	56.2	0.316	0.363	7.08	2.16 ± 0.24	++
8	0.079	1.91	0.288	<0.010	61.7	0.085	0.085	>100	3.55	+++
9	<0.010	<0.010	<0.010	0.014	0.041	<0.010	<0.010	<0.010	0.112 ± 0.066	++++
10	<0.005	0.575	<0.005	1.20	2.04	0.091	0.015	4.57	0.382 ± 0.119	++
11	1.78	1.15	0.040	0.030	74.1	0.813	0.155	67.6	4.64 ± 1.25	++++
12	26.3	72.4	18.2	37.2	34.7	NT	>100	>100	50.1	++
13	<0.005	<0.005	<0.005	5.01	5.75	0.126	<0.005	0.977	0.243 ± 0.088	+++
14	18.2	1.48	17.8	15.1	15.1	11.5	10.7	>100	12.0	+
15	0.427	0.120	0.100	1.29	0.832	0.257	0.182	1.74	0.766 ± 0.254	+
16	<0.005	0.214	0.145	0.457	5.01	0.145	0.081	2.63	0.715 ± 0.335	+++
17	9.77	2.34	1.44	1.23	15.1	>100	0.275	>100	7.86 ± 0.27	++
18	<0.005	<0.005	0.550	0.162	0.525	1.48	0.603	1.95	1.27 ± 0.84	+++
19	2.69	1.41	2.34	0.79	1.66	1.66	1.41	2.75	1.86	++++
20	< 0.010	< 0.010	< 0.010	< 0.010	< 0.010	< 0.010	< 0.010	0.014	0.059 ± 0.026	+++
21	0.19	0.274	0.016	0.012	0.864	0.015	0.017	2.17	0.370 ± 0.28	++++

The cytotoxicity GI50 values are the concentrations corresponding to 50% growth inhibition.

Mean graph midpoint for growth inhibition of all human cancer cell lines successfully tested. Compounds with standard deviations listed for the MGM values were tested twice, while those without standard deviations for the MGM values were tested once.

The compounds were tested at concentrations ranging up to 10 μM. The activity of the compounds to produce Top1-mediated DNA cleavage was expressed semi-quantitatively as follows: +: weak activity; ++: similar activity as the parent compound 1; +++ & ++++: greater activity than the parent compound 1; ++++: similar activity as 1 μM camptothecin.