Sinteza i antiproliferativna ispitivanja novih derivata iminokumarina

master's thesis

• Title (english): Synthesis and antiproliferative evaluations of novel iminocoumarin derivatives
• Author: Nikolina Kalčec
• Mentor: Tatjana Gazivoda Kraljević (mentor)
• Committee member: Tatjana Gazivoda Kraljević (predsjednik povjerenstva)
• Committee member: Dragana Mutavdžić Pavlović (član povjerenstva)
• Committee member: Lidija Furač (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2018-09-27, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry; Organic Chemistry

Abstract

Poznavajući važnost iminokumarina i farmakološka svojstva 1,2,3-triazola, sinteza novih derivata iz okosnica njihove strukture važna je u razvoju novih spojeva s potencijalnom antitumorskom aktivnošću. U ovom radu opisana je sinteza novih C-4 alkinilnih derivata benzaldehida (3, 4) i C-5 alkinilnih derivata salicilaldehida (5-7) Sonogashira-inom reakcijom unakrsnog povezivanja, triazolnih derivata salicilaldehida (23-27) te derivata iminokumarina 28-37. Mikrovalovima potpomognutom klik reakcijom 5-azidometilsalicilaldehida 21 s odgovarajućim terminalnim alkinima uz bakar kao katalizator sintetizirani su 1,2,3-triazolni derivati salicilaldehida 23-27, koji reakcijom s 2-(1H-benzo[d]imidazol-2-il)acetonitrilom u apsolutnom etanolu i piperidinu daju 1,2,3-triazolne derivate iminokumarina 28-30. Reakcijom kondenzacije salicilaldehida s 2-(1H-benzo[d]imidazol-2-il)acetonitrilom u apsolutnom etanolu i piperidinu nastaje derivat iminokumarina 31, koji in situ reakcijom s NaN3, terminalnim alkinom, Et3N i CuSO4 u otopini tert-butanol : H2O (1 : 1) daje triazolni derivat iminokumarina 33. Mikrovalovima potpomognutom klik reakcijom 6-azido iminokumarinskog derivata (34) s odgovarajućim terminalnim alkinima pripravljeni su 6-(1,2,3-triazolilni) derivati iminokumarina 35 i 37. Strukturna karakterizacija novosintetiziranih spojeva provedena je 1H-NMR spektroskopijom. Farmakološki učinci i moguće biološke mete predviđeni su in silico analizom (PASS). Antiproliferativna in vitro ispitivanja novosintetiziranih spojeva ispitat će se na staničnim tumorskim linijama porijeklom iz čovjeka.

Abstract (english)

Due to importance of iminocoumarine and farmacological properties of 1,2,3-triazole development of novel derivatives from their backbones is important for development of novel compounds with potential antitumor activity. This work presents the synthesis of C-5 alkynyl benzaldehyde (3 ,4) derivatives and C-5 alkynyl salicylaldehyde (5-7) derivatives by Pd-catalysed Sonogashira cross-coupling reaction, triazole derivative of salicylaldehyde (23-27) as well as iminocoumarin derivatives 28-37. Cu-catalyzed click reactions under microvawe irradiation of 5-azidomethylsalicylicaldehyde 21 with corresponding alkynes, 1,2,3-triazole salicylaldehyde derivatives 23-27 were obtained, which are then converted to 1,2,3-triazole iminocoumarin derivatives 28-30 by reaction with 2-(1H-benzo[d]imidazol-2-yl)acetonitrile in absolute ethanol and piperidine. Condensation reaction of salicylaldehyde and 2-(1H-benzo[d]imidazol-2-yl)acetonitrile in absolute ethanol and piperidine, iminocumarin derivative 31 was obtained, which are then converted to 1,2,3-triazole iminocoumarin derivative 33 by in situ reaction with NaN3, terminal alkyne, Et3N and CuSO4 in a solution of tert-butanol: H2O (1 : 1). Microwave assisted click reaction of 6-azido iminocoumarin derivative (34) and corresponding terminal alkynes gave 6-(1,2,3-triazolyl) iminocoumarin derivatives 35 and 37. Structural characterization of novel compounds was conducted using 1H-NMR spectroscopy. Pharmacological effects and possible biologycal targets were predicted using in silico analysis (PASS). Antiproliferative evaluation will be preformed in vitro against human malignant tumor cells.

• Keywords: Sonogashira-ina reakcija; salicilaldehid; klik kemija; 1 2 3-triazolni derivati iminokumarina; in silico analiza
• Keywords (english): Sonogashira cross-coupling; salicylaldehyde; click chemistry; 1 2 3-triazole iminocoumarin derivatives; in silico analysis
• Language: croatian
• URN:NBN: urn:nbn:hr:149:147422
• Study programme: Title: Applied Chemistry - Graduate study; specializations in: Environmental chemistry and green technologies, Advanced materials and technologies, Applied organic chemistry; Course: Applied organic chemistry; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra primijenjene kemije (magistar/magistra primijenjene kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2020-10-29 12:02:49