Ispitivanje stabilnosti amidino supstituiranih derivata benzotiazola spektrometrijom masa visoke razlučivosti

master's thesis

• Title (english): Stability testing of amidino substituted benzothiazole derivatives by high resolution mass spectrometry
• Author: Ivan Lukač
• Mentor: Dragana Mutavdžić Pavlović (mentor)
• Committee member: Dragana Mutavdžić Pavlović (predsjednik povjerenstva)
• Committee member: Tatjana Gazivoda Kraljević (član povjerenstva)
• Committee member: Lidija Furač (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2020-09-25, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

Uz nezamjenjivu ulogu koju farmaceutici imaju u medicini važno je imati na umu često negativni efekt koji njihova proizvodnja i ispuštanje imaju na okoliš. Nepoznati spojevi koji predstavljaju potencijalne nove farmaceutske proizvode je s toga važno proučavati s obzirom na nedostatak eksperimentalnih podataka koji postoje o njihovoj mogućoj štetnosti za okoliš i zdravlje ljudi. Kako bi se maksimalno zaštitili okoliš i ljudsko zdravlje pri proizvodnji, uporabi i zbrinjavanju farmaceutika važno je dobiti što bolje rezultate o njihovoj mogućoj štetnosti. Problem leži u tome što je broj novih organskih spojeva koji se sintetiziraju u industriji ogroman, a klasična testiranja su skupocjena, dugotrajna i potencijalno etički problematična s obzirom na uporabu testnih životinja. S toga se sve više nastoji računalno procijeniti potencijalna štetnost novih spojeva. Za procjenu moguće štetnosti, promatrani novosintetizirani spojevi LD-1 i LD-2, amidino supstituirani derivati benzotiazola, izloženi su oksidacijskim, kiselim i lužnatim uvjetima te UV/VIS zračenju i povišenim temperaturama kako bi došlo do njihove prisilne razgradnje. Tako tretirani uzorci su se zatim analizirali pomoću 2D-UHPLC-QTOF sustava i iz dobivenih kromatograma i spektra masa pretpostavljeni su njihovi razgradni produkti te predloženi razgradni putevi. Početni spojevi LD-1 i LD-2 kao i njihovi potencijalni razgradni produkti podvrgnuli su se testiranju primijenom T.E.S.T. programskog paketa s ciljem procijene bioakumulacijskog faktora, razvojne toksičnosti i mutagenosti. T.E.S.T. je programski paket kojeg je američka agencija za zaštitu okoliša izdala kao besplatni softver za procjenu opasnosti organskih kemikalija da ugroze zdravlje ljudi ili oštete okoliš. Matematički modeli koje metode procjene u T.E.S.T.-u uspoređuju analizirane molekule s poznatim molekulama u bazi podataka na temelju velikog broja fizičkih deskriptora. Ovaj pristup omogućuje brzu, jeftinu i jednostavnu procjenu opasnosti neke molekule za zdravlje ljudi ili okoliš.

Abstract (english)

With the irreplaceable role which pharmaceuticals have in medicine it is important to keep in mind the frequently negative effects of their production and release can have on the environment. Unknown compounds which represent potentially new pharmaceutical products are therefore important to study given the lack of experimental data that exists for their potential harmfulness to the environment and the health of humans. In order to maximally protect the environment and human health in the production, usage and disposal of pharmaceuticals it is important to get the best possible results about their harmfulness. The problem lies in the fact that the number of new organic compounds synthesized in the industry is enormous and classical testing is expensive, time consuming and potentially ethically problematic in regards to the usage of test animals. Hence there is a striving to use computational estimates of potential harmfulness of new compounds. For the estimation of the possible harmfulness of the new synthetized compounds LD-1 and LD-2, amidino substituted benzothiazoles, they were exposed to oxidative, acidic and basic conditions in addition to being exposed to UV/VIS radiation and high temperatures in order to bring about their forced degradations. Samples treated in such a way were analyzed with the help of a 2D-UHPLC-QTOF system and from the resulting chromatograms and mass spectra their degradation products are assumed and degradation pathways were suggested. The starting compounds LD-1 and LD-2 as well as their potential degradation products were analyzed using T.E.S.T. software package in order to estimate the bioaccumulation factor, developmental toxicity and mutagenicity. T.E.S.T. is a program package which the American environmental protection agency has released for free as a piece of software for the estimation of the danger organic chemicals pose to human health and the environment. The mathematical models which the estimation methods incorporated into T.E.S.T. compare the analyzed molecules with known molecules in the database based on a large number of physical descriptors. This approach allows for quick, cheap and simple risk estimates of a molecule for human health or the environment.

• Keywords: amidino supstituirani benzotiazoli; forsirana razgradnja; T.E.S.T.; procjena toksičnosti
• Keywords (english): amidino substituted benzothiazoles; forced degradation; T.E.S.T.; toxicity estimation
• Language: croatian
• URN:NBN: urn:nbn:hr:149:866018
• 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: Environmental Engineering - Graduate study; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka ekoinženjerstva (magistar/magistra inženjer/inženjerka ekoinženjerstva)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2021-06-18
• Created on: 2020-10-28 09:32:09