prikaz prve stranice dokumenta Sinteza harmizinina amidnog tipa u položajima O-7 i N-9 β-karbolinskog prstena
  Download
PDF 1.63 MB
master's thesis
Sinteza harmizinina amidnog tipa u položajima O-7 i N-9 β-karbolinskog prstena
Zagreb: University of Zagreb, Faculty of Pharmacy and Biochemistry, 2022. urn:nbn:hr:163:595909
Gregorić, Magdalena
University of Zagreb
Faculty of Pharmacy and Biochemistry
Department of medicinal chemistry

Institutional repository: Repository of Faculty of Pharmacy and Biochemistry University of Zagreb

Cite this document

Gregorić, M. (2022). Sinteza harmizinina amidnog tipa u položajima O-7 i N-9 β-karbolinskog prstena (Master's thesis). Zagreb: University of Zagreb, Faculty of Pharmacy and Biochemistry. Retrieved from https://urn.nsk.hr/urn:nbn:hr:163:595909

Gregorić, Magdalena. "Sinteza harmizinina amidnog tipa u položajima O-7 i N-9 β-karbolinskog prstena." Master's thesis, University of Zagreb, Faculty of Pharmacy and Biochemistry, 2022. https://urn.nsk.hr/urn:nbn:hr:163:595909

Gregorić, Magdalena. "Sinteza harmizinina amidnog tipa u položajima O-7 i N-9 β-karbolinskog prstena." Master's thesis, University of Zagreb, Faculty of Pharmacy and Biochemistry, 2022. https://urn.nsk.hr/urn:nbn:hr:163:595909

Gregorić, M. (2022). 'Sinteza harmizinina amidnog tipa u položajima O-7 i N-9 β-karbolinskog prstena', Master's thesis, University of Zagreb, Faculty of Pharmacy and Biochemistry, accessed 18 December 2024, https://urn.nsk.hr/urn:nbn:hr:163:595909

Gregorić M. Sinteza harmizinina amidnog tipa u položajima O-7 i N-9 β-karbolinskog prstena [Master's thesis]. Zagreb: University of Zagreb, Faculty of Pharmacy and Biochemistry; 2022 [cited 2024 December 18] Available at: https://urn.nsk.hr/urn:nbn:hr:163:595909

M. Gregorić, "Sinteza harmizinina amidnog tipa u položajima O-7 i N-9 β-karbolinskog prstena", Master's thesis, University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, 2022. Available at: https://urn.nsk.hr/urn:nbn:hr:163:595909

Metadata
TitleSinteza harmizinina amidnog tipa u položajima O-7 i N-9 β-karbolinskog prstena
Title (english)Synthesis of amide-type harmisinins in the positions O-7 and N-9 of the beta-carboline ring
AuthorMagdalena Gregorić
MentorZrinka Rajić (mentor)
Committee memberZrinka Rajić (predsjednik povjerenstva)
Committee memberHrvoje Rimac (član povjerenstva)
Committee memberAnita Hafner (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Pharmacy and Biochemistry
(Department of medicinal chemistry)
Zagreb
Defense date and country2022-06-20, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Pharmacy
Pharmacy
Abstract
Artemizinin i njegovi derivati predstavljaju najznačajniju skupinu lijekova u borbi protiv malarije. S obzirom da je pojava rezistencije na dosad poznatu terapiju protiv malarije veliki globalni problem, potrebno je kontinuirano istraživati nove potencijalne lijekove. Cilj ovog diplomskog rada bila je sinteza harmizinina, hibridnih spojeva dviju molekula poznatih antimalarijskih svojstava, artezunata i harmina, za koje se pretpostavlja da bi mogli pokazati pojačano antimalarijsko djelovanje. Sinteza hibridnih spojeva uključivala je reakciju povezivanja artezunata i amina harmina 2 ili 6, uz coupling reagens i bazu. Reakciji povezivanja prethodila je sinteza amina 2 i 6, pripravljenih u položajima N-9 i O-7 β-karbolinskog prstena u nekoliko koraka počevši od komercijalno dostupnog harmina. Novosintetizirani harmizinini karakterizirani su uobičajenim analitičkim i spektroskopskim metodama te su im pomoću programa SwissADME određene vrijednosti farmakokinetičkih parametara koji predviđaju lošu GIT apsorpciju i upitnu oralnu bioraspoloživost ovih molekula. Nadalje, program predviđa kako su harmizinini potencijalni supstrati P-glikoproteina i potencijalni inhibitori enzima CYP3A4. Daljnjim istraživanjima, koji nadilaze okvire ovog diplomskog rada, sintetiziranim harmizininima 3 i 7 bit će ispitano antimalarijsko i antiproliferativno djelovanje.
Abstract (english)
Artemisinin and its derivatives are the most important drugs in the fight against malaria. Since the emergence of resistance to the known antimalarial drugs is a major global problem, new potential drugs need to be constantly explored. The aim of this diploma thesis was the sythesis of harmisinins, hybrid compounds prepared by covalently linking two molecules with known antimalarial properties, artesunate and harmine, which are thought to have antimalarial activity. The synthesis of hybrid compounds was carried out by coupling reaction of artesunate and harmine-based amine 2 or 6, with coupling reagent and base. The coupling reaction was preceded by the synthesis of amines 2 and 6, which were prepared starting from commercial harmine in several steps at the N-9 and O-7 positions of the β-carboline ring. Newly synthesized harmisinins were characterized by standard analytical and spectroscopic methods. The SwissADME program was used to determine values of their pharmacokinetic parameters, which predicted poor GIT absorption and questionable oral bioavailability of these molecules. In addition, the program predicted that harmisinins are potential substrates of P-glycoprotein and potential inhibitors of CYP3A4 enzyme. In further research, beyond the scope of this diploma thesis, synthesized harmizinins 3 and 7 will be evaluated for their antimalarial and antiproliferative activity.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:163:595909
Study programmeTitle: Pharmacy
Study programme type: university
Study level: integrated undergraduate and graduate
Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Embargo expiration date: 2024-06-20
Terms of useLicence In copyright icon
Created on2022-07-15 12:53:27