Compound | R5 | R7 | a/b |
Min. DNA un-winding conc.a
(μg/mL) |
Decatanation inhib.b
(μg/mL) |
A549c
CC50 (μg/mL) |
P388d
CC50 (μg/mL) |
P388/
ADRe (MDR) CC50 (μg/mL) |
---|---|---|---|---|---|---|---|---|
56j | H | B | H/H | 3 | 2 | 0.59 | 0.04 | 0.39 |
57 | H | C | H/H | 128 | >100 | 2 | 0.5 | * |
58 | H | A | H/Me | * | * | 0.12 | 0.038 | 0.24 |
59 | H | A | Me/Me | * | * | 0.034 | 0.012 | * |
60 | H | A | H/OMe | * | * | 0.29 | 0.05 | * |
61 | H | A | H/Ph | * | * | 0.16 | 0.07 | * |
62 | NH2 | A | H/H | * | * | 0.069 | 0.0053 | * |
63 | NH2 | B | H/H | * | * | 0.10 | 0.0047 | * |
64 | NHMe | A | H/H | * | * | 0.39 | 0.039 | * |
65 | NH2 | D | H/H | * | * | 0.06 | 0.030 | * |
66 | NHMe | D | H/H | * | * | 1.1 | 0.79 | * |
67 | NMe2 | D | H/H | * | * | 6.4 | 3.9 | * |
a Measured at 10mM MgCl2; b drug concentration that inhibits 50% of the conversion of catenated to decatenated k-DNA catalyzed by calf thymus topoisomerase II; c human breast cancer cell line; d murine leukemia cell line; e adriamycin resistant/multidrug resistant; f doxorubicin (adriamycin); g 55 = A-62176 (racemate); h R-enantiomer of 55; i S-enantiomer of 55; j 56 = A-74932 (diasteromeric mixture); *data not reported.