Citotoksičnost i antioksidacijska aktivnost kvaternih amonijevih spojeva piridinijeva-4-aldoksima

master's thesis

• Title (english): Cytotoxicity and antioxidative activity of quaternary ammonium compounds of pyridine-4-aldoxime
• Author: Tajana Perić
• Mentor: Matilda Šprung (mentor)
• Mentor: Martina Šeruga Musić (sumentor)
• Committee member: Martina Šeruga Musić (predsjednik povjerenstva)
• Committee member: Dubravko Pavoković (član povjerenstva)
• Committee member: Zoran Marčić (član povjerenstva)
• Committee member: Tvrtko Dražina (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2020-02-28, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Kvaterni amonijevi spojevi (QAC) amfifilni su antimikrobni lijekovi široke primjene u
mnogim industrijskim okruženjima. Zbog svoje široke upotrebe i kemijske stabilnosti, ovi
spojevi dugo se zadržavaju u okolišu, što rezultira razvojem bakterijske rezistencije. S ciljem
rješavanja ovog problema, mnoge su znanstveno-istraživačke skupine pokušale modificirati
strukturu komercijalno dostupnih QAC-ova, ali samo nekoliko studija do sada objavilo je
sintezu QACs kemijskom pretvorbom prirodnih prekursora. Kao strukturni dio mnogih
prirodnih proizvoda, piridinski prstenovi dugo su bili inspiracija sintetičkim kemičarima. Stoga
je u središtu ovog diplomskog rada istraživanje biološkog potencijala novo sintetiziranih QACova
izvedenih iz piridina. Antioksidativna aktivnost procijenjena je dvjema neovisnim
metodama in vitro, a to su kapacitet za apsorbciju kisikovih radikala (ORAC) i metoda
oksidativnog oštećenja molekule DNA, otkrivajući N-benzil-4-hidroksiiminometilpiridinij
fluorid (Py-4-BnF) kao spoj s najboljim antioksidativnim potencijalom. Citotoksičnost ovih
spojeva prema zdravim ljudskim staničnim linijama, HaCat i RPE1, sugerira da su spojevi
potencijalno sigurni za ljude i da bi mogli predstavljati dobro polazište za razvoj novih QAC-a
u primjeni protiv gljivica. Antimikrobna aktivnost ovih spojeva ispitana na kulturama bakterija
Escherichia coli i Staphylococcus aureus pokazala je nešto niži antibakterijski potencijal.

Abstract (english)

Quaternary ammonium (QACs) are amphiphilic antimicrobials with wide application in
many different industrial environments. Due to their widespread use and chemical stability,
these compounds retain in the environment for a longer periods of time resulting in the
development of bacterial resistance. To overcome this problem, many scientific research groups
have attempted to modify structure of commercially available QACs, but only few studies so
far report QACs synthesized from the natural precursors. As a structural part of many natural
products, pyridine rings have long been an inspiration for synthetic chemists. Therefore, in the
scope of this diploma thesis is an investigation of the biological potential of newly synthesized
QACs derived from pyridine. The antioxidative activity was assessed by two independent in
vitro methods, namely Oxygen Radical Absorbance Capacity (ORAC) and DNA nicking
assays, revealing candidate N-benzyl-4-hydroxiiminomethylpyridinium fluoride (Py-4-BnF)
with the best antioxidative potential. The cytotoxicity of these compounds toward healthy
human cell lines, HaCat and RPE1, suggests that compounds are potentially safe for humans
and that they might present a good starting point for development of new QACs with antifungal
application. The antimicrobial activity testing of new compounds against Escherichia coli and
Staphylococcus aureus revealed low antibacterial potential.

• Keywords: kvaterni amonijevi spojevi; piridin; N-benzil-4-hidroksiiminometilpiridinij bromid; N-benzil-4-hidroksiiminometilpiridinij fluorid; antioksidans; antimikrobnost; citotoksičnost
• Keywords (english): Quaternary ammonium compounds; pyridine; N-benzyl-4- hydroxiiminomethylpyridinium bromide; N-benzyl-4-hydroxiiminomethylpyridinium fluoride; antioxidans; antimicrobial activity; cytotoxicity
• Language: croatian
• URN:NBN: urn:nbn:hr:217:268179
• Study programme: Title: Experimental Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra eksperimentalne biologije (magistar/magistra eksperimentalne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2020-07-13 07:11:38