Ispitivanje stabilnosti amino supstituiranih benzimidazo[1,2-a]kinolina spektrometrijom masa visoke razlučivosti

master's thesis

• Title (english): Stability investigation of amino substituted benzimidazo[1,2-a]quinolines by high resolution mass spectrometry
• Author: Mia Gotovuša
• Mentor: Dragana Mutavdžić Pavlović (mentor)
• Committee member: Dragana Mutavdžić Pavlović (predsjednik povjerenstva)
• Committee member: Marijana Hranjec (član povjerenstva)
• Committee member: Lidija Furač (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2020-09-14, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

Znanstvena istraživanja u području organske kemije i biokemije u novije su vrijeme usmjerena pronalaženju odgovarajućih sintetskih mehanizama kojima bi se dobili spojevi poželjne biološke aktivnosti. Potencijalnim kemoterapeuticima pokazali su se heterociklički spojevi, konkretno u ovom radu ispitivani derivati spojeva iz skupine benzimidazola. Ovi spojevi posjeduju biološki aktivna svojstva uslijed mehanizma interkalacije kojem podliježu u reakcijama s biološkim makromolekulama, poput deoksiribonukleinske kiseline, ribonukleinske kiseline i proteina. Postupak istraživanja i razvoja ovih lijekova podrazumijeva provedbu eksperimenata prisilne razgradnje, u okolišnim uvjetima u kojima se oni mogu naći tijekom transporta i skladištenja. Hidrolitička, termalna, fotolitička te razgradnja u prisutnosti vodikovog peroksida eksperimentalni su postupci kojima su se u ovom radu podvrgnuli novosintetizirani spojevi. Nastali razgradni produkti detektirani su i identificirani primjenom spektrometrije masa visoke razlučivosti, a pripadajuće strukturne formule dobivene su primjenom računalnog programa ChemDRAW. Nad dobivenim strukturama primijenjeni su i računalni modeli u sklopu programa TEST, u cilju procjene bioakumulacijskog faktora, toksičnosti i mutagenosti analiziranih spojeva.

Abstract (english)

In recent years, scientific research in the field of organic chemistry and biochemistry has mainly focused on finding appropriate synthetic mechanisms by which the compounds of desirable biological activity can be obtained. Heterocyclic compounds have been proven to be potential chemotherapeutics, specifically the benzimidazole derivatives of the compounds tested in this thesis. These compounds possess biologically active properties due to the intercalation mechanism which they are subject to in reactions with biological macromolecules, such as deoxyribonucleic acid, ribonucleic acid and proteins. The process of research and development of these drugs involves the implementation of forced degradation experiments, in the environmental conditions in which they can be found during transport and storage. Hydrolytic, thermal, photolytic and degradation in the presence of hydrogen peroxide are experimental methods to which the newly synthesized compounds were subjected. The detection and identification of resulting degradation products was performed using high-resolution mass spectrometry, and the corresponding structural formulas were obtained with the application of a software ChemDRAW. Computer models within the TEST program were applied to the obtained structures, in order to assess the bioaccumulation factor, toxicity and mutagenicity of the analysed compounds.

• Keywords: benzimidazoli; prisilna razgradnja; razgradni produkti; bioakumulacijski faktor; toksičnost; mutagenost
• Keywords (english): benzimidazoles; forced degradation; degradation products; bioaccumulation factor; toxicity; mutagenicity
• Language: croatian
• URN:NBN: urn:nbn:hr:149:439331
• Project: Number: IP-2018-01-4379; Title: Istraživanje antioksidativnog djelovanja benzazolskog skeleta u dizajnu novih antitumorskih agensa; Acronym: AntioxPot; Leader: Marijana Hranjec; Jurisdiction: Croatia; Funder: HRZZ; Funding stream: IP
• Study programme: Title: Chemical Engineering - Graduate study; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka kemijskog inženjerstva (magistar/magistra inženjer/inženjerka kemijskog inženjerstva)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2021-06-18
• Created on: 2022-03-02 14:18:03