Bisantrene didrochloride is a highly effective antitumor agent, it exerts its cytotoxicity by affecting DNA intercalation. Bisantrene didrochloride targets eukaryotic type II topoisomerases. Bisantrene didrochloride is a substrate of MDR1[1][2][3][4].
Bisantrene didrochloride promots DNase I cleavage at oligopurine-oligopyrimidine tracts and slightly reduces the cleavage activity at alternating purine-pyrimidine sequences[1].
Bisantrene didrochloride is an inhibitor of [3H]uridine incorporation into RNA and [3H]tmidine incorporation into DNA[2].
Bisantrene didrochloride is an antitumor agent active against a number of experimental tumors, including P388 leukemia, L1210 leukemia, Lieberman plasma cell tumor, B16 melanoma, colon tumor 26, and Ridgway osteogenic sarcoma[3].
Bisantrene didrochloride is effective over a dose range of 1.56 to 150 mg/kg depending upon the frequency, route, and schedule of the treatment and the tumor model used[3].
Bisantrene didrochloride (25, 50 and 100 mg/kg; i.p.; once) pretreats with macrophages shows antitumor effect to mice with P815 tumor cells injection[3].
Bisantrene didrochloride (10-150 mg/kg; i.v.; once) dose-dependently induces leukopenia in Neo mice. B cells and macrophages are targets for bisantrene didrochloride toxicity[4].
[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 , et al. Bisantrene, an active new drug in the treatment of metastatic breast cancer. Cancer Res. 1983 Mar;43(3):1402-4.
[3]. Wang BS, et al. Activation of tumor-cytostatic macrophages with the antitumor agent 9,10-anthracenedicarboxaldede bis[(4,5-didro-1H-imidazole-2-yl)drazone] didrochloride (bisantrene). Cancer Res. 1984 Jun;44(6):2363-7.
[4]. Aksentijevich I, et al. Retroviral transfer of the human MDR1 gene confers resistance to bisantrene-specific hematotoxicity. Clin Cancer Res. 1996 Jun;2(6):973-80.