Derivati harmina kao potencijalni inhibitori bakterijskog biofilma

master's thesis

• Title (english): Harmine derivatives as potential biofilm inhibitors
• Author: Katja Kapović
• Mentor: Zrinka Rajić (mentor)
• Committee member: Zrinka Rajić (predsjednik povjerenstva)
• Committee member: Ivana Perković (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: 2020-10-05, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Biofilm je zajednica različitih vrsta mikroorganizama koji su uklopljeni u matriks. Matriks predstavlja fizičku
barijeru koja otežava penetraciju antibiotika do ciljnih stanica, a s druge strane, zbog viskoelastičnosti otežano je
mehaničko uklanjanje. Navedeno čini biofilm kako zdravstvenim, tako i industrijskim problemom s obzirom da se
može formirati na bilo kojoj metalnoj ili plastičnoj površini. U ovom radu sintetizirana su tri potencijalna inhibitora
biofilma (6-8). Sinteza se odvijala u četiri koraka, a kao početni spoj uzet je harmin. U prvom koraku sinteze
Michaelovom adicijom dobiven je ester 1. U idućem koraku u reakciji hidrolize dobivena je kiselina 2. U trećem
koraku sinteze reakcijom couplinga između kiseline 2 i odgovarajućeg amina (4-amino-1-Boc-piperidina, 4-(NBoc-
amino)piperidina ili N-Bocetilendiamina), uz HATU/DIEA dobiveni su N-Boc zaštićeni amidi (3-5). Boc
zaštitna skupina uklonjena je u kiselim uvjetima, uz TFA, te su dobiveni odgovarajući amidi (6-8). Spojevima su
određena su tališta, a njihove strukture potvrđene su standardnim spektroskopskim i spektrometrijskim tehnikama
(IR, 1H i 13C NMR, MS). U daljnjim istraživanjima, bit će ispitano njihovo inhibitorno djelovanje na bakterijski
biofilm.

Abstract (english)

Biofilm is a community consisting of various types of microorganisms embedded in extracellular matrix, which
represents a physical barrier that complicates antibiotic penetration to target bacteria. Furthermore, mechanical
removal is complicated due to viscoelastic properties of biofilm. Aforementioned makes biofilm a major
healthcare, as well as industrial problem, due to the fact that it can be formed on any metal or plastic surface. Three
potential biofilm inhibitors have been synthetized (6-8). Synthesis was done in a four step procedure using harmine
as a starting compound. The first step included Michael reaction resulting in esther 1, which was subsequently
hydrolised to give acid 2. The third step included coupling reaction between acid 2 and corresponding amine (4-
amino-1-Boc-piperidine, 4-(N-Boc-amino)piperidine or N-Boc-ethylenediamine), in the presence of
HATU/DIEA, resulting in N-Boc protected amides (3-5). Boc protective group was removed under acid conditions,
(TFA), to yield final compounds, amides (6-8). Melting points of new compounds were determined and their
structures were confirmed using standard spectroscopic and spectrometric techniques (IR, 1H and 13C NMR, MS).
Their inhibitory activity on bacterial biofilm will be tested in further studies.

• Keywords: harmin; biofilm; coupling; sinteza
• Keywords (english): harmine; biofilm; coupling; synthesis
• Language: croatian
• URN:NBN: urn:nbn:hr:163:916342
• 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; Embargo expiration date: 2022-10-05
• Created on: 2022-03-02 13:55:37