|
|
New inhibitors of topoisomerase II - study of antiproliferative effects and influence on antitumor activity of etoposide
Proftová, Lenka ; Šimůnek, Tomáš (advisor) ; Macháček, Miloslav (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Lenka Ohnemichlová 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 etoposide Cancer is a serious societal health problem, which can affect each of us, and its incidence increases rapidly with age. Anthracycline antibiotics (ANT) are extremely effective drugs that have been used to treat a number of cancers. They have a multimodal mechanism of action, one of them being the inhibition of topoisomerase 2 (TOP2), an essential cellular enzyme modulating DNA topology. Currently, use of ANTs is limited due to concerns about the occurrence of cardiotoxicity. Etoposide (ETO) is an antitumor agent that acts as topoisomerase poison. ETO is often used in combination therapy with ANTs, but it is not considered significantly cardiotoxic. Dexrazoxane (DEX) is the only approved cardioprotectant against cardiotoxicity of ANTs. However, it does not act as chelating agent, as previously thought, but through inhibition of TOP2. Although DEX has been shown to be a very potent cardioprotectant, it also has its disadvantages. DEX has been associated with the occurrence of secondary...
|
guest ::
