Work

Coenzyme Q10 as an Inhibitor of Effector Release from One-Electron-Reduced Bioreductive Anticancer Prodrugs

Year: 2025

Type: article

Abstract: The kinetic parameters for the release of anticancer effectors from the radical anions of prodrugs through fragmentation have been measured under conditions that model the interfacial region where the enzymatic reduction in the prodrugs takes place. While the back-oxidation of the radical anions via O2 mainly occurs under normoxia, preventing radical anion fragmentation, this is not the case for the lower concentrations of O2 found in hypoxic regions of tumors. Rate-constant data show that O2 concentrations known to bring about a 50% decrease in the level of cell kill arising from the prodrugs in anoxia (the K-value) do not significantly inhibit the fragmentation of radical anions. Evidence is put forward suggesting that radical anions can undergo an electron transfer to ubiquinone (CoQ10, UQ) in competition with the fragmentation of the radical anions releasing effectors. The prior inhibition of the synthesis of UQ in cells is put forward as a possible approach to increase the effectiveness of such prodrugs in killing hypoxic tumor cells.

Source: Molecules

DOI: 10.3390/molecules30040760

Authors: Robert F. Anderson, Wen Qi

Institutions: University of Auckland, Maurice Wilkins Centre

Language: English

Topic: Bioactive Compounds and Antitumor Agents

Subfield: Toxicology

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,258