Sinteza i karakterizacija hibrida artezunata i β-karbolina

master's thesis

• Title (english): Synthesis and characterization of artezunate β-carboline hybrid
• Author: Neva Kravaršćan
• Mentor: Zrinka Rajić (mentor)
• Committee member: Zrinka Rajić (predsjednik povjerenstva)
• Committee member: Hrvoje Rimac (član povjerenstva)
• Committee member: Maja Ortner Hadžiabdić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of medicinal chemistry); Zagreb
• Defense date and country: 2022-08-30, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Otkriće artemizina označilo je prekretnicu u terapiji malarije, čemu svjedoči preporuka SZO da se ACT koristi kao prva linija u liječenju ove bolesti. Međutim, pojava rezistentnih sojeva plazmodija ugrožava učinkovitost terapije, zbog čega je potrebno kontinuirano razvijati nove antimalarike. Jedan od pristupa u dizajniranju i razvoju novih lijekova je molekulska hibridizacija koja podrazumijeva povezivanje dvije biološki aktivne molekule u jedinstveni kemijski entitet, odnosno hibridnu molekulu. Racionalnim odabirom roditeljskih molekula moguće je pripraviti hibrid koji djeluje na različite mete zbog čega ostvaruje snažnije djelovanje te neće doći do razvoja rezistencije. U okviru ovog diplomskog rada pripravljen je hibrid artezunata, polusintetskog derivata artemizinina i harmina, β-karbolinskog alkaloida s izraženim antimalarijskim djelovanjem korištenjem reakcije povezivanja uz coupling reagens HATU i bazu DIEA (spoj 6). Za potrebe sinteze hibrida, sintetiziran je i amin 5, u pet reakcijskih koraka. Struktura konačnog spoja potvrđena je uobičajnim analitičkim i spektroskopskim metodama (IR, MS, 1H i 13C NMR). U nastavku istraživanja pripravljenom hibridu bit će ispitano antimalarijsko i protutumorsko djelovanje.

Abstract (english)

The discovery of artemisinin was a breakthrough in the treatment of malaria leading to the recommendation of the WHO to use ACT as the first-line therapy against malaria. Nevertheless, the occurrence of drug-resistant Plasmodium strains challenges its efficency and urges the need for constant development of new antimalarials. One of the approaches in the discovery of new bioactive agents is molecular hybridization, which represents synthesis of novel chemical entities (hybrid molecule) by forming covalent bond between two biologically active molecules. Rational selection of parent molecules enables the preparation of a hybrid with improved properties. Within this Master Thesis, hybrid (6) comprising artesunate, semisynthetic derivative of artemizinin and harmine, β-carboline alkaloid with pronounced antimalarial activity, was prepared by coupling reaction using HATU and DIEA. For the purpose of the hybrid synthesis, amine 5 was synthesized as well, through five reaction steps. The structure of novel compound was confirmed using standard analytical and spectroscopic methods (IR, MS, 1H i 13C NMR). Antimalarial and antiproliferative activity of the synthesized hybrid 6 will be evaluated in the future studies.

• Keywords: malarija; artemizinin; harmin; amid; hibridna molekula; reakcija povezivanja
• Keywords (english): malaria; artemisinin; harmine; amide; hybrid molecule; coupling reaction
• Language: croatian
• URN:NBN: urn:nbn:hr:163:361755
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2024-08-30
• Created on: 2022-09-05 13:57:06