Correlation between the topoisomerase I-mediated activity and growth-inhibitory activity for saintopin-type antibiotics
| Compound | Topoisomerase I-mediated DNA cleavage activity2-a | Protein/DNA complex formation in HeLa S3 cells2-b | Effect on DNA2-c | Growth inhibition (IC50)2-d |
|---|---|---|---|---|
| Camptothecin | 0.12 | 0.081 | No activity | 0.095 |
| UCE6 | 0.073 | 0.033 | No activity | 0.09 |
| Saintopin | 0.25 | 1.4 | Unwinding | 1.20 |
| Saintopin E | 0.4 | >10 | No activity | >10 |
| UCE1022 | 2.1 | 4.0 | Unwinding | >10 |
↵2-a The concentrations of drugs (μm) that produce nicked DNA at a yield of 20% of substrate DNA in cell-free assay (purified enzyme assay system) (see Fig. 2).
↵2-b The concentrations of drugs (μm) that precipitate 10% of total trichloroacetic acid-precipitable cpm in cell based assay (potassium/SDS precipitation method) (see Table 1).
↵2-c The DNA-binding properties were measured using DNA (un)winding assay as described in Materials and Methods. Unwinding, unwinding property; No activity, no (un)winging property at concentration of ≤100 μm (see legend to Fig. 5 and Ref.11).
↵2-d The growth-inhibitory activities against HeLa S3 cells were expressed by the IC50, the concentrations of drugs (μm) required for 50% inhibition of cell growth over 72 hr of exposure. Cell growth was quantified by absorbance measurement (at 630 nm) in the microtiter plate assay as described in Materials and Methods.