Sinteza hidroksamske kiseline hibrida primakina i cimetne kiseline

master's thesis

• Title (english): Synthesis of primaquine-cinammic acid hybrid with hydroxamic acid moiety
• Author: Goran Poje
• Mentor: Zrinka Rajić Džolić (mentor)
• Committee member: Zrinka Rajić Džolić (predsjednik povjerenstva)
• Committee member: Branka Zorc (član povjerenstva)
• Committee member: Višnja Drinovac (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of medicinal chemistry); Zagreb
• Defense date and country: 2018-06-29, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Novija istraživanja pokazuju da su epigenetske modifikacije jednako bitne u procesu razvoja tumora kao i
mutacije gena. Posebno se ističu acetilacije, odnosno deacetilacije jer utječu na strukturu kromatina čime
određuju gensku ekspresiju. U tumorskih stanica uočena je prekomjerna aktivnost histonskih deacetilaza
(HDAC) koje uklanjaju ε-acetilnu skupinu iz bočnih aminokiselinskih ogranaka lizina. Dolazi do utišavanja
tumorsupresorskih gena te aktivacije gena koji potiču preživljavanje i proliferaciju stanica tumora. Lijekovi
inhibitori HDAC kompleksiraju ione cinka iz aktivnog mjesta enzima. Prema kemijskoj strukturi dijelimo ih u
četiri skupine, od kojih su najzanimljivije hidroksamske kiseline zbog visoke sposobnosti keliranja iona metala i
inhibicije HDAC-a.
Cilj ovoga diplomskog rada bila je sinteza hibridnog derivata primakina i cimetne kiseline s terminalnom
hidroksamskom kiselinom, za kojeg se pretpostavlja da bi, zbog svojih strukturnih karakteristika, mogao imati
antimalarijsko i/ili citostatsko djelovanje. Isprobane su tri sintetske metode, no unatoč tome, sinteza ciljne
molekule nije bila uspješna.

Abstract (english)

Recent research shows that carcinogenesis cannot be explained only by genetic alterations, but also involves
epigenetic modifications. In particular acetylation and deacetylation affect the structure of chromatin which
determines gene expression. In tumor cells excessive activity of histone deacetylases (HDAC), enzymes that
remove the ε-acetyl group from the lateral lysine amino acid residues, was observed. It results in suppression of
tumor-suppressor genes and activation of genes that stimulate survival and proliferation of tumor cells. HDAC
inhibitors complex zinc ions found in the enzyme's active site. According to the chemical structure, they are
divided into four groups, of which hydroxamic acids are the most interesting ones, due to their high metal ion
chelating ability.
The goal of this diploma thesis was the synthesis of a hybrid derivative primaquine and cinnamic acid with
terminal hydroxamic acid moiety, which might, due to the structural characteristics, exert cytostatic and/or
antimalarial activity. Although three synthetic methods were employed, synthesis of the target compound was
not achieved.

• Keywords: HDAC inhibitori; hidroksamska kiselina; primakin; cimetna kiselina; sinteza
• Keywords (english): HDAC inhibitors; hydroxamic acid; primaquine; cinnamic acid; synthesis
• Language: croatian
• URN:NBN: urn:nbn:hr:163:196243
• 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: 2019-01-16 09:53:26