Ispitivanje antioksidativne i prooksidativne aktivnosti odabranih jedinjenja fenolnog tipa

Abstract

Izvod: Mnoga prirodna polifenolna jedinjenja se smatraju dobrim antioksidantima. Od kada je uočeno da igraju ključnu ulogu u odbrambenom mehanizmu bioloških sistema, njima se pridaje još veći značaj. Iako se u prirodi može naći širok spektar jedinjenja ovog tipa, zbog različitih ljudskih potreba javlja se sve veće interesovanje za specifičnijim antioksidantima fenolnog tipa, zbog čega se na njihovoj sintezi danas intenzivno radi. Međutim, iako se pokazalo da sintetički antioksidanti pokazuju izuzetne osobine i imaju značajnu primenu (npr. u prehrambenoj industriji), mora se voditi računa o njihovom potencijalnom štetnom efektu. U poslednjoj dekadi se značajna pažnja posvećuje rasvetljavanju dualističkog antioksidativno-prooksidativnog ponašanja prirodnih i sintetičkih fenolnih i polifenolnih jedinjenja. Naime, pokazalo se da se pod određenim in vitro uslovima neka fenolna i polifenolna jedinjenja, ponašaju kao dobri antioksidanti, dok se u ćeliji, odnosno normalnom biološkom okruženju, ponašaju na drugačiji način. U ćelijskoj sredini ova jedinjenja, najčešće, ispoljavaju prooksidativno dejstvo, tj. indukuju hiperprodukciju aktivnih kiseoničnih vrsta, pre svega superoksid anjon radikala. U okviru ove disertacije ispitane su antioksidativne i prooksidativne osobine fenolnih jedinjenja. Kako bi se ispitali mehanizmi antiradikalskog delovanja prirodnih jedinjenja fenolnog tipa urađena je analiza galne kiseline kao njihovog predstavnika. Takođe, metodama teorije funkcionala gustine ispitana je antiradikalska aktivnost sintetisanih Šifovih baza. U cilju eksperimentalnog ispitivanja antioksidativne aktivnosti dobijenih fenolnih jedinjenja (Šifovih baza) korišćeni su DPPH test i inhibicija enzima lipoksigenaza, dok je njihova prooksidativna aktivnost testirana in vitro na ćelijskim linijama primarnog kancera debelog creva i sekundarnog kancera dojke, kao i na zdravim ćelijama MRC-5.

Summary: Many natural polyphenolic compounds are considered to be good antioxidants. Since it has been noticed that they play an important role in the defense mechanism of biological systems, they are given even greater significance. Although a wide range of compounds of this type can be found in nature, because of different human needs, there is an increasing interest in synthesis of more specific antioxidants of the phenolic type, which is why their synthesis is in focus these days. However, although synthetic antioxidants have been shown to exhibit exceptional traits and have significant application (e.g. in the food industry), their potentially harmful effects must be taken into account. In the last decade, considerable attention was devoted to illumination of dualistic antioxidative-proxidative behavior of natural and synthetic phenolic and polyphenolic compounds. Namely, certain in vitro conditions have shown that some phenolic and polyphenolic compounds behave as good antioxidants, whereas they behave in a different way in a cell or a natural biological environment. Most frequently, in the cellular environment these compounds exhibit a prooxidative effect, i.e. induce hyperproduction of active oxygen species, primarily superoxide anion radicals. Within this dissertation the antioxidative and protoxidative properties of phenolic compounds were examined. In order to investigate mechanisms of antiradical action of natural compounds of the phenolic type, analysis of gallic acid as their representative was performed. Also, the methods of density functional theory (DFT) were applied for the investigation of the antiradical activity of the synthesized Schiff bases. For the purpose of experimental testing of the antioxidant activity of the obtained phenolic compounds (Schiff bases), DPPH and lipoxygenase enzyme inhibition were used, while their prooxidative activity was tested in vitro on the cell lines of the primary colon cancer and secondary breast cancer, as well as on healthy MRC-5 cells . The obtained results are of scientific importance because they contribute to the clarification of the antioxidative and/or antiradical behavior of phenolic compounds and their in vitro tested prooxidative or cytotoxic action.