Sinteza in vrednotenje antioksidativne kapacitete izbranih kinazolinonov : magistrski študijski program Laboratorijska biomedicina

Škulj, Zala (author), Mravljak, Janez (mentor)

Antioksidanti so katere koli snovi, ki upočasnijo, odstranijo ali preprečijo nastanek reaktivnih zvrsti in oksidativnih poškodb molekul. Reaktivne zvrsti, ki nastajajo tako endogeno kot eksogeno, so vpletene v nastanek številnih bolezni, zato so raziskave za učinkovitejše in varnejše antioksidante izrednega pomena. Namen magistrske naloge je sinteza različnih analogov kinazolinonov, ki jih bomo ovrednotili z DPPH testom. Ugotavljali bomo, kako število in prisotnost različnih skupin vplivata na antioksidativno kapaciteto spojin. S postopkom aerobne oksidativne ciklizacije v DMSO, ki je izredno uporaben postopek, saj ni potrebe po uporabi dodatnih reagentov, smo pripravili različne kinazolinone, ki so na mestu 2 substituirani s polifenoli. Nato smo z DPPH testom, ki temelji na uporabi stabilnega radikala 1,1-difenil-2-pikril-hidrazila (DPPH), ovrednotili antioksidativno kapaciteto spojin. DPPH sprejme vodikov atom iz antioksidanta, kar privede do redukcije 1,1-difenil-2-pikril-hidrazila v 1,1-difenil-2-pikril-hidrazin (DPPH-H). Pri redukciji se vijolična barva DPPH molekule spremeni v rumeno, kar se spektrofotometrično odraža s padcem absorbance pri 517 nm. Rezultate se najpogosteje izrazi kot koncentracijo antioksidanta, ki je potrebna za redukcijo 50% začetne koncentracije DPPH (EC50). Ugotovili smo, da na antioksidativno kapaciteto vpliva tako število kot tudi položaj hidroksilnih skupin. Največjo antioksidativno kapaciteto izkazujeta derivata z dvema prostima hidroksilnima skupinama, saj lahko donirata 2 vodikova atoma in s tem nevtralizirata 2 molekuli DPPH. Derivata z eno hidroksilno skupino ne delujeta kot antioksidanta. Ugotovili smo, da prisotnost ene metoksi skupine zveča antioksidativno kapaciteto, prisotnost dveh metoksi skupin pa nekoliko zmanjša antioksidativno kapaciteto. Prav tako smo ugotovili, da zamenjava fenilnega obroča s stirilom zveča antioksidativno kapaciteto, zamenjava metoksi skupine z etoksi skupino pa antioksidativno kapaciteto le malenkost zveča. Derivata z dvema hidroksilnima skupinama, ki imata veliko antioksidativno kapaciteto, sta potencialno zanimiva za rabo v medicini in farmaciji, vendar pa bi bilo treba opraviti še dodatne in vitro ali tudi in vivo teste za nadaljnje ugotavljanje antioksidativnih lastnosti.

• Language: Slovenian
• Keywords: oksidativni stres prosti radikali kinazolinoni DPPH 1, 1-difenil-2-pikril-hidrazil
• Work type: Master's thesis/paper
• Typology: 2.09 - Master's Thesis
• Organization: FFA - Faculty of Pharmacy
• Place of publishing: Ljubljana
• Publisher: [Z. Škulj]
• Year: 2018
• Number of pages: VIII, 54 str.
• PID: 20.500.12556/RUL-120361
• UDC: 616:577.334(043.3)
• COBISS.SI-ID: 4468593
• Publication date in RUL: 18.09.2020

Secondary language

• Language: English
• Title: Synthesis and evaluation of antioxidative capacity of selected quinazolinones

Abstract

Antioxidants are all compounds that decelerate, remove or prevent emergence of reactive species and oxidation injuries of molecules. The reactive species that are created in an endogenous or exogenous way are involved in the emergence of many diseases. This is why the researches for more effective and safe antioxidants are of great importance. The purpose of this thesis is the synthesis of different quinazolinones, which will be evaluated with DPPH test. We will evaluate how the antioxidative capacity of the tested compounds is effected by the number and presence of different groups. With aerobic oxidative cyclization in DMSO we prepared different quinazolinones which are substituted with polyphenols on the position 2. Since the protocol does not use any other additives and generates only water as a by-product, the aerobic oxidative cyclization is a very useful method. With DPPH test, which is based on the use of stable radical 1,1-diphenyl-2-picrylhydrazyl (DPPH), we evaluated the antioxidative capacity. DPPH molecule removes hydrogen atom from the potential antioxidant which leads to reduction of 1,1-diphenyl-2-picrylhydrazyl into 1,1-diphenyl-2-picrylhydrazine (DPPH-H). Reduction causes colour alternation from violet to yellow and the fall of absorption at 517 nm which can be detected with spectrophotometry. The results are usually represented as concentration of antioxidant necessary for reduction of initial DPPH concentration by 50% (EC50 value). We discovered that the number and the position of hydroxide groups affect the antioxidative capacity. Derivatives with two hydroxide groups have the greatest antioxidant capacity as they donate two hydrogen atoms and can therefore neutralise two molecules of DPPH. Derivatives with one hydroxide group show no antioxidative activities. We discovered that the presence of one methoxy group increases the antioxidative capacity, while presence of two methoxy groups somewhat decreases it. We also discovered that the replacement of phenyl with styryl increases the antioxidative capacity and the replacement of methoxy group with ethoxy group increases antioxidative capacity a little bit. Derivatives with two hydroxide groups that have the greatest antioxidant capacity are interesting for the use in medicine and pharmacy; however more in vitro and in vivo tests must be done for further evaluation of antioxidative properties.

• Keywords: antioxidants radicals DPPH quinazolinones