Sinteza novih urea i semikarbazidnih derivata primakina

master's thesis

• Title (english): Synthesis of new urea and semicarbazide derivatives of primaquine
• Author: Tomislav Ubrekić
• Mentor: Ivana Perković (mentor)
• Committee member: Ivana Perković
• Committee member: Branka Zorc
• Committee member: Miranda Sertić
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of medicinal chemistry); Zagreb
• Defense date and country: 2015-07-09, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Primakin je poznati antimalarik i polazni spoj u dizajniranju mnogih potencijalno biološko aktivnih spojeva. U prethodnim istraživanjima otkrivena je i citostatska aktivnost urea i semikarbazidnih derivata primakina. Primakinski semikarbazidi i uree su pokazali visoku selektivnost na MCF-7 stanične linije (karcinom dojke). Cilj ovog rada bio je sintetizirati urea i semikarbazidne derivate primakina s različitim supstituentima na benzenskoj jezgri. U sintezama je korištena benzotriazolska metoda prethodno razvijena na Zavodu za farmaceutsku kemiju. Početni spoj korišten u sintezi je klorid 1-benzotriazolkarboksilne kiseline (BtcCl, 1). Reakcijom BtcCl (1) i odgovarajućeg anilina dobiveni su 1-karbamoilbenzotriazoli 2a-c. Urea derivati 3a-c dobiveni su u reakciji primakina s odgovarajućim 1-karbamoilbenzotriazolom 2a-c, a semikarbazidni derivati 6a-c u reakciji primakinskog semikarbazida 5 s odgovarajućim 1-karbamoilbenzotriazolom 2a-c. Strukture svih sintetiziranih spojeva potvrđene su uobičajenim spektroskopskim metodama (IR, 1H i 13C NMR, MS) te je svim čvrstim produktima određeno talište. Sintetiziranim derivatima primakina u daljnjim će istraživanjima biti ispitano antitumorsko djelovanje.

Abstract (english)

Primaquine is a well known antimalarial drug and interesting molecule for design of potentially biologically active substances. In previous researchs urea and semicarbazide derivatives of primaquine has been proven as antitumor agents and showed high selectivity towards MCF-7 cell line (breast carcinom). The purpose of this research was the synthesis of new urea and semicarbazide derivatives with various substituents on the benzene ring. The benzotriazole methodology that was developed on Department of Medicinal Chemistry was used for synthesis of primaquine derivatives. The starting compound, chloride of benzotriazole carboxylic acid (BtcCl, 1), reacted with corresponding anilines to prepare 1-carbamoylbenzotriazoles 2a-c. Urea derivatives 3a-c were prepared by reaction of primaquine diphosphate with corresponding 1-carbamoylbenzotriazoles 2a-c, and the semicarbazide derivatives 6a-c by reaction of primaquine semicarbazide 5 with 1-carbamoylbenzotriazoles 2a-c. Structures of all synthesized compounds were determined by usual spectroscopic methods (IR, 1H and13C NMR, MS) and melting points were determined. Antitumor activity screening of the synthesized primaquine derivatives is in progress.

• Keywords: primakin; semikarbazid; urea; sinteza
• Keywords (english): primaquine; semicarbazide; urea; synthesis
• Language: croatian
• URN:NBN: urn:nbn:hr:163:051502
• 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: Open access
• Created on: 2016-03-02 10:43:45