Table 17. Banyu eukaryotic and prokaryotic biochemical and cellular data for enantiomers 116 and 125 and in vivo antitumor activities in 3 murine models. Etoposide and ciprofloxacin were used as controls.
In vitro or in vivo assay |
14
etopo-side |
15
cipro-floxacin |
||
---|---|---|---|---|
E. coli gyrase DNA supercoiling IC50 (μg/ml)a | 0.2 | 1.0 | * | 1.0 |
L1210 topo II DNA relaxation IC50 (μg/ml)a | 1.5 | 24 | 4.4 | > 50 |
L1210 topo II induction of DNA cleavage IC50 (μg/ml)a |
1.2 | > 12 | ½ as active vs of (-)-BO | * |
L1210 topo II induction of DNA cleavable complex formation in intact cells IC50 (μg/ml)a | 3-17 fold increase vs control over range 0.10 to 28 μg/ml |
minimal complex formation at 9 μg/ml | ½ as active vs of (-)-BO | * |
P388 cytotoxicity CC50 (μg/ml)a |
0.004 | 0.50 | 0.004 | * |
L1210 cytotoxicity CC50 (μg/ml)a |
0.017 | 1.7 | 0.020 | * |
Antitumor activity i.p.-implanted murine leukaemia P388 0.313mg/kg/day i.p. | ||||
Survival days mean: | 16.4b | * | 22.2b | * |
T/C%c | 146 | * | 198 | * |
Antitumor activity on i.p.-implanted murine leukaemia L1210 0.313mg/kg/day i.p. | ||||
Survival days mean: | 21.2d | * | 31.4d | * |
T/C%: | 155 | * | 229 | * |
Antitumor activity on s.c.-implanted colon 26 solid tumor 1.25 mg/kg/day s.c. | ||||
Tumor weight mean (g): | 0.00e | * | 1.28e | * |
% inhibition | 100 | * | 63 | * |
aValues originally reported as μM were converted to μg/ml for this table; bcontrol = 11.2 days; cRatio (%) of survival time of drug treated animals to control; dcontrol = 13.7 days; econtrol tumor weight mean = 3.46g.