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1/2 Abstract Charles University Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Candidate: Manuela Voráčová Supervisors: Prof. RNDr. Milan Pour, PhD Adj. Prof. Paula Kiuru, PhD Title: Synthesis of natural product analogues as potential antitumour agents Keywords: combretastatin, combretafuranone, purpurealidin, cytotoxic, KV10.1 inhibitors, analogue synthesis Despite numerous efforts and advances in prevention, diagnostics and treatment of human malignancies, cancer is still one of the leading causes of mortality worldwide. In the search for novel drug candidates, the rich biodiversity in the nature remains a valuable source of lead structures. Combretastatin A-4 (CA4) isolated from Combretum caffrum tree and purpurealidin I isolated from marine sponge Pseudoceratina purpurea are examples of such structures that served as an inspiration in the synthesis of potential anti-cancer agents within my thesis work. Combretastatin A-4 is a well-known suppressor of tubulin polymerization via interaction with the colchicine binding site. It causes inhibition of cell growth and concurrently acts as a vascular disrupting agent and angiogenesis inhibitor. Being a cis stilbene derivative, it can readily isomerize into a thermodynamically more stable, but less active trans form... |
