Sinteza i karakterizacija novih 1,2,3-triazolnih derivata harmina i cimetne kiseline

master's thesis

• Title (english): Synthesis and characteriztion of novel harmine and cinnamic acid 1,2,3-triazole derivates
• Author: Gea Martinović
• Mentor: Ivana Perković (mentor)
• Committee member: Ivana Perković (predsjednik povjerenstva)
• Committee member: Zrinka Rajić (član povjerenstva)
• Committee member: Ana Mornar Turk (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of medicinal chemistry); Zagreb
• Defense date and country: 2019-08-30, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Ovaj rad dio je istraživanja provedenog na Zavodu za farmaceutsku kemiju Farmaceutsko-biokemijskog
fakulteta Sveučilišta u Zagrebu koji obuhvaća dizajniranje, sintetiziranje i biološku evaluaciju derivata
harmina s antimalarijskim djelovanjem. Cilj ovog rada bila je sinteza i karakterizacija dosad neopisana
četiri 1,2,3-triazolna derivata harmina koji u svojoj strukturi sadrže derivate cimetne kiseline.
Sinteza je započeta prevođenjem derivata cimetne kiseline do odgovarajućih azida (3a,b) prema dolje
navedenoj shemi, a harmin i harmol, alkohol nastao demetiliranjem harmina, prevedeni su u odgovarajuće
alkine (5 i 6) u reakciji s propargil bromidom. Bakar (I)-katalizirajućom azid-alkin ciklizacijom u kojoj su
početni reaktanti bili azidi derivata cimetne kiseline (3a,b) i alkini (5 i 6) dobiveni su konačni produkti 7a,b
i 8a,b.
Strukture svih sintetiziranih spojeva potvrđene su uobičajenim spektroskopskim metodama (IR, 1H i 13C
NMR, MS). Čvrstim produktima određeno je talište. Sva četiri spoja zadovoljavaju Lipinskijeva i Veberova
pravila, a dobru oralnu bioraspoloživost predviđa im i alat SwissADME.
Sintetiziranim derivatima će u daljnjim istraživanjima biti ispitano biološko djelovanje.

Abstract (english)

This paper is a part of ongoing reaserch at the Department of Medicinal Chemistry, Faculty of Pharmacy and
Biochemistry, University of Zagreb. Main focus of the research is design, synthesis and biological evaluation
of novel harmine derivates as potential antimalarial drugs. The aim of this diploma thesis was the synthesis
and characterization of four novel harmine 1,2,3-triazole derivates containing cinnamic acid derivates in their
structure.
Synthesis began with transformation of cinnamic acid derivates to azides (3a,b) in a four step procedure. On
the other hand, harmine and harmole (4), an alcohol generated by demethylation of harmine, were transformed
in alkynes 5 and 6, in the reaction of alkylation using propargyl bromide. The copper(I)-catalyzed azidealkyne cycloaddition, in which cinnamic acid derivates azides (3a,b) and alkynes (5 and 6) were used, resulted
in the formation of final compounds 7a,b (N-derivatives) and 8a,b (O-derivatives).
Structures of the newly prepared compounds were confirmed using conventional analytical and spectroscopic
methods (IR, 1H and 13C NMR, MS). Melting points of the solid compounds were also determined.
All four novel derivatives meet all of the Lipinski and Veber criteria for good oral bioavailability of potential
drugs. SwissADME web tool predicts good oral bioavailability of all four derivatives.
Further studies will investigate antimalarial activity of the new harmine derivatives.

• Keywords: harmin; cimetna kiselina. 1; 2; 3- triazol; sinteza
• Keywords (english): harmine; cinnamic acid; 1; 2; 3-triazoles; synthesis
• Language: croatian
• URN:NBN: urn:nbn:hr:163:986279
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2020-02-21 15:06:05