Insa Klemt, Viktor Reshetnikov, Subrata Dutta, Galyna Bila, Rostyslav Bilyy, Itziar Cossío Cuartero, Andrés Hidalgo, Adrian Wünsche, Maximilian Böhm, Marit Wondrak, Leoni A Kunz-Schughart, Rainer Tietze, Frank Beierlein, Petra Imhof, Sabrina Gensberger-Reigl, Monika Pischetsrieder, Marlies Körber, Tina Jost, Andriy Mokhir
Many known chemotherapeutic anticancer agents exhibit neutropenia as a dose-limiting side effect. In this paper we suggest a prodrug concept solving this problem for camptothecin (HO-cpt). The prodrug is programmed according to Boolean "AND" logic. In the absence of H2 O2 (trigger T1), e.g. in the majority of normal cells, it exists as an inactive oligomer. In cancer cells and in primed neutrophils (high H2 O2 ), the oligomer is disrupted forming intermediate (inactive) lipophilic cationic species. These are accumulated in mitochondria (Mit) of cancer cells, where they are activated by hydrolysis at mitochondrial pH 8 (trigger T2) with formation of camptothecin...
April 24, 2024: RSC medicinal chemistry