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. Author manuscript; available in PMC: 2013 Dec 27.
Published in final edited form as: J Med Chem. 2012 Dec 7;55(24):10844–10862. doi: 10.1021/jm300519w

Table 1.

Antiproliferative Potencies and Topoisomerase I Inhibitory Activities of Hydroxyindenoisoquinolines.

Compd Cytotoxicity (GI50 in μM)a
MGMb Top1 Cleavagec
lung HOP-62 Colon HCT-116 CNS SF-539 melanoma UACC-62 Ovarian OVCAR-3 renal SN12C prostate DU-145 breast MCF-7
157 0.01 0.03 0.01 0.01 0.22 0.02 0.01 0.01 0.040±0.0187d ++++
457 1.3 35 41 4.2 73 68 37 1.58 20.0 ± 14 ++
546 0.02 0.10 0.04 0.03 0.5 <0.01 <0.01 <0.01 0.21±0.19 ++++
646 <0.01 <0.01 0.04 <0.01 0.08 <0.01 <0.01 0.01 0.079±0.023 +++++
746 1.78 1.15 0.04 0.03 74.1 0.813 0.155 0.37 4.64±1.25 +++++
14a >100 >100 − 0.331 >100 − >100 0.05 41.8±7.15 ++(+)
14b 0.180 2.34 0.282 0.07 8.32 0.191 0.204 0.03 3.07±0.32 +++
22a <0.01 <0.01 <0.01 <0.01 0.02 <0.01 <0.01 <0.01 0.055±0.003 ++++(+)
22b 0.02 0.03 0.02 0.02 0.03 0.02 0.02 0.02 0.087±0.063 +++++
35a <0.01 0.02 <0.01 0.03 0.07 <0.01 <0.01 − 0.049 +++++
35b 0.257 0.279 0.335 0.282 0.871 0.195 0.257 0.144 0.412±0.005 ++(+)
44a <0.01 <0.01 <0.01 <0.01 0.03 <0.01 <0.01 <0.01 0.043 ++++
44b 0.01 0.02 <0.01 <0.01 0.03 <0.01 <0.01 <0.01 0.056 +++(+)
45a 0.549 1.35 0.479 0.372 1.95 0.501 0.407 0.427 1.66 ++
45b 2.09 2.40 2.40 0.776 4.79 3.39 2.63 0.646 3.16 ++
52a 0.04 0.229 0.01 <0.01 0.407 0.03 0.100 0.02 0.224 ++
52b 0.371 0.407 0.148 0.078 0.501 0.065 0.490 0.050 0.602 ++++
a

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

b

Mean graph midpoint for growth inhibition of all human cancer cell lines successfully tested, ranging from 10−8 to 10−4 molar.

c

Compound-induced DNA cleavage due to Top1 inhibition is graded by the following rubric relative to 1 μM camptothecin: 0, no inhibitory activity; +, between 20 and 50% activity; ++, between 50 and 75% activity; +++, between 75% and 95% activity; ++++, equipotent, +++++ more potent.

d

For MGM GI50 values in which a standard error appears, the GI50 values for individual cell lines are the average of two determinations; values without standard error are from one determination. The values for 1, 4, 5, 6, and 7 are from many determinations.