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Synthesis of dexrazoxane analogues as potential cardioprotectants II
 Kratochvíl, Marek ; Roh, Jaroslav (advisor) ; Nováková, Veronika (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Kralove Department of Inorganic and Organic Chemistry Candidate: Marek Kratochvíl Supervisor: PharmDr. Jaroslav Roh, PhD. Title of diploma thesis: Syntesis of dexrazoxane analogues as potential cardioprotectants II ! Doxorubicin, daunorubicin and other anthracycline antineoplastic antibiotics are very important anticancer agents. Due to their high toxicity in the heart muscle, these highly effective drugs are often associated with acute cardiotoxicity and dose-dependent cardiomyopathy. This cardiomyopathy is characterized by enlargement of the left ventricle and complete systolic dysfunction. It is assumed that this side effect is mainly caused by reactive oxygen species, whose formation is catalysed by complex of anthracyclines and iron ions. The only clinically used drug that significantly reduce anthracycline cardiotoxicity is dexrazoxane (DEX). DEX is in vivo metabolised to a substance ADR-925, which chelates the iron ions. DEX is also a catalytic inhibitor of topoisomerase II (TOP2). Interestingly, the cardioprotective effects of DEX were discovered accidentally and only few structure-cardioprotective activity relationships studies were published. The aim of this work was to develop a method for the preparation of DEX analogue 4,4'-...
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