Activation of the anticancer drugs cyclophosphamide and ifosfamide by cytochrome P450
- G. Vredenburg, S. den Braver-Sewradj, B.M.A. van Vugt-Lussenburg, N.P.E. Vermeulen, J.N.M. Commandeur, J. C. Vos
- BM3 mutants. Toxicology Letters 2015,
Acrolein is a toxic metabolite of the anticancer agent cyclophosphamide (CP). Current strategies to mitigate acrolein toxicity are insufficient, and in this brief article, we report the synthesis of well-defined low molecular weight block copolymers using activators generated by electron transfer atom transfer radical polymerization (AGET ATRP) capable of reacting with the cytotoxic small molecule acrolein. Acrolein reactivity was introduced into the block copolymers via incorporation of either (a) aminooxy or (b) sulfhydryl groups. The cytoprotective effect of the polymers was compared to sodium 2-sulfanylethanesulfonate (mesna) the current gold standard for protection from CP urotoxicity, and we found that the polymers bearing sulfhydryl moieties demonstrated superior cytoprotective activity.