TABLE 2

Activities in inducing TOP1-mediated DNA damage, cytotoxicity, and RS of the six INDO derivatives Activity of each INDO derivative in inducing TOP1-mediated DNA cleavage in vitro (second column) or covalent protein-DNA cross-links in CHO cells (third column) was denoted as high (+++), modest (++), or low (+), based on Fig. 4. Cytotoxic activity of each INDO derivative is based on the LD50 (drug concentration leading to 50% cell death) determined graphically from clonogenic survival assays in the CHO cells as described under Materials and Methods. The drug treatment time was 1 h. RS activity of each INDO derivative was based on experiments conducted in the MCF-7 (as shown in Fig. 2) and DC3F cells (as shown in TABLE 4). + indicates RS activity; - indicates no RS activity.

INDO derivatives TOP1-Mediated DNA Cleavagea Protein-DNA Cross-Linksb Cytotoxicityc RSd
μg/ml
F1 + ++ 5.0 ± 0.3 +
F5 + + >10 +
F7 +++ ++ 7.3 ± 0.2 +
F43 + + >10
F44 ++ ++ 2.4 ± 0.2
F71 +++ +++ 2.0 ± 0.4