Ametantrone

Ametantrone is an inhibitor of topoisomerase II.¹ It induces double-strand breaks in SV40 DNA in the presence, but not absence, of topoisomerase II and induces single-strand breaks in DNA in NCI H187 cells.^1,2 It also induces interstrand DNA cross-links in HeLa S3 cells at a minimum concentration of 4.1 µM.³ Ametantrone is cytotoxic to NCI H187 and HL-60 cells (IC₅₀s = 112 and 0.44 µM, respectively). It inhibits tumor growth in a Ridgway osteogenic sarcoma mouse model when administered at a dose of 5 mg/kg, however, it increases tumor growth in mouse models of mammary adenocarcinoma and colon adenocarcinoma 11a.⁴

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1. De Isabella, P., Capranico, G., Palumbo, M., et al. Sequence selectivity of topoisomerase II DNA cleavage stimulated by mitoxantrone derivatives: Relationships to drug DNA binding and cellular effects. Mol. Pharmacol. 43(5), 715-721 (1993).

2. De Isabella, P., Palumbo, M., Sissi, C., et al. Topoisomerase II DNA cleavage stimulation, DNA binding activity, cytotoxicity, and physico-chemical properties of 2-aza- and 2-aza-oxide-anthracenedione derivatives. Mol. Pharmacol. 48(1), 30-38 (1995).

3. Skladanowski, A., and Konopa, J. Mitoxantrone and ametantrone induce interstrand cross-links in DNA of tumour cells. Br. J. Cancer. 82(7), 1300-1304 (2000).

4. Leopold, W.R., Nelson, J.M., Plowman, J., et al. Anthrapyrazoles, a new class of intercalating agents with high-level, broad spectrum activity against murine tumors. Cancer Res. 45(11 Pt 1), 5532-5539 (1985).