Synthesis and characterization of triazole type O-harmicines at the position 7 of the β-carboline ring

Harmin i derivati cimetne kiseline su prirodni produkti koji pokazuju širok spektar bioloških djelovanja, među kojima su antimalarijsko i citostatsko djelovanje. Njihovim kovalentnim povezivanjem u hibridne spojeve, harmicine, nastoji se postići poboljšano djelovanje, smanjenje neželjenih učinaka i interakcija te smanjenje rezistencije na postojeću farmakoterapiju. U okviru ovog diplomskog rada sintetizirani su O-harmicini triazolskog tipa, 6a-e, korištenjem Cu(I) katalizirane alkin-azid cikloadicije. Usto, sintetizirani su i polazni spojevi, azidi derivata cimetne kiseline 3a-e i alkin 5. O-harmicini 6a-e su karakterizirani uobičajenim analitičkim i spektroskopskim metodama (talište, IR, 1H i 13C NMR, MS). U daljnjim istraživanjima sintetiziranim spojevima će biti ispitano citostatsko djelovanje na nizu tumorskih staničnih linija.Harmine and cinnamic acid derivatives are natural products with a broad spectrum of biological activities, which includes antimalarial and cytotoxic effects. By their covalent binding to hybrid molecules, harmicines, improved action, reduction of side effects, drug interactions and resistance to existing pharmacotherapy might be achieved. In this thesis, O-harmicines of the triazole type 6a-e were synthesised using the Cu(I)-catalyzed dipolar alkyne-azide cycloaddition. Starting compounds, cynnamyl azides 3a-e and alkyne 5 were synthesized as well. Structures of O-harmicines were confirmed using conventional analytical and spectroscopic methods (melting point, IR, 1H and 13C NMR, MS). Further studies will focus on the evaluation of their cytotoxic activity against several cancer cell lines