Work

Interactions of pixantrone with apurinic/apyrimidinic sites in DNA

Year: 2024

Type: article

Abstract: Pixantrone and mitoxantrone are structurally related anticancer drugs which have been shown to generate covalent conjugates at apurinic/apyrimidinic (AP) sites in DNA. Mitoxantrone binding to AP sites induces DNA strand cleavage and inhibits the endonuclease activity of human AP endonuclease 1 (APE1). Here, pixantrone was demonstrated to have similar properties, but relative to mitoxantrone, it was significantly less potent in both DNA incision and APE1 inhibition. Consistent with these observations, pixantrone had ~ 15-fold lower affinity for DNA containing an AP site analogue, tetrahydrofuran, as measured by a Thiazole Orange (ThO) displacement assay.

Source: PubMed Central

DOI: 10.17912/micropub.biology.001207

Authors: Irina G. Minko, Michael M. Luzadder, Amanda K. McCullough, R. Stephen Lloyd

Institution: Oregon Health & Science University

Language: English

Topic: Cancer therapeutics and mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Cancer Institute