Nové inhibitory topoisomerasy II - studie antiproliferačních účinků a vlivu na protinádorovou aktivitu anthracyklinů

Vrobelová, Adriana

Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Adriana Vrobelová Supervisor: prof. PharmDr. Tomáš Šimůnek, PhD. Title of diploma thesis: New inhibitors of topoisomerase II - study of antiproliferative effects and influence on antitumor activity of anthracyclines Despite the dose-limiting cardiotoxicity, anthracyclines (ANT) are among the most effective and widely used antitumor drugs. The only registered drug to prevent this adverse effect is dexrazoxane, whose cardioprotective activity is currently attributed to interaction with topoisomerase 2 (TOP2) beta. This relatively new hypothesis provides an opportunity for the discovery and study of new TOP2 inhibitors, that could be more beneficial cardioprotective drugs. An essential condition for the use of a potential cardioprotective agent is, however, the absence of a negative influence on anticancer efficacy. In this work, we studied the antiproliferative activity of new substances derived from the molecule BNS-22, which is a catalytic inhibitor of TOP2 and manifested cardioprotective activity. We also studied the activity against the antiproliferative effect of daunorubicin (DAU), to clarify the compatibility in case of combined use. These experiments were performed on the leukocytic cell...

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