Bisantrene is a highly effective antitumor drug, targets eukaryotic type II topoisomerases.
Bisantrene shows an outstanding ability to form a complex with DNA. Bisantrene exhibits the most effective binding (even neglecting electrostatic contacts), followed by the 9-substituted compounds and finally by 1-IHA. Bisantrene congeners retained a remarkable capacity for binding to the single-stranded structure. In comparison with the Ki values found for double-stranded DNA, 9-IHA shows a 2-fold increase, 1-IHA maintains the same values, and aza-9-IHA exhibits a modest reduction. On the other hand, Bisantrene, although undergoing a 6-fold reduction in Ki, still exhibits an affinity constant of the order of 106 M-1. Bisantrene promots DNase I cleavage at oligopurine-oligopyrimidine tracts; conversely, it slightly reduces the cleavage activity at alternating purine-pyrimidine sequences[1]. Bisantrene is an active new drug in the treatment of metastatic breast cancer. Bisantrene is an inhibitor of [3H]uridine incorporation into RNA and [3H]thymidine incorporation into DNA[2].
References:
[1]. Sissi C, et al. DNA-binding preferences of Bisantrene analogues: relevance to the sequence specificity of drug-mediated topoisomerase II poisoning. Mol Pharmacol. 1998 Dec;54(6):1036-45.
[2]. Yap HY, et al. Bisantrene, an active new drug in the treatment of metastatic breast cancer. Cancer Res. 1983 Mar;43(3):1402-4.