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Synthesis and in vitro evaluation of novel iron chelators based on salicylaldehyde isonicotinoyl hydrazone
Kubeš, Jan ; Roh, Jaroslav (advisor) ; Krátký, Martin (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Author: Jan Kubeš Supervisors: doc. PharmDr. Jaroslav Roh, PhD. PharmDr. Hana Jansová, PhD. Title of Diploma Thesis: Synthesis and in vitro evaluation of novel iron chelators based on salicylaldehyde isonicotinoyl hydrazone Iron ions (Fe) are required in many vital processes. However, this transition metal may also catalyze reactions which results in the formation of toxic reactive oxygen species (ROS), e.g. Haber- Weiss reaction producing highly toxic hydroxyl radicals. Salicylaldehyde isonicotinoyl hydrazone (SIH) is a tridental chelator selectively forming complexes with Fe ions. As a result of its low molecular weight and good lipophilicity, SIH can be administered orally. It readily enters the cells, effectively chelates the intracellular Fe ions, and is therefore able to very efficiently inhibit the Fe dependent processes, such as production of ROS, but also the synthesis of some proteins and enzymes and the processes they regulate (e.g., cellular growth and proliferation). In this work we focused on the design, synthesis and in vitro evaluation of novel SIH analogues, in particular the thio analogue of SIH (thioSIH, A), analogues derived from (di)hydroxybenzophenone (B) and...
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