Mono- i bis-1,2,3-triazolilni derivati benzimidazo[1,2-a]kinolina: sinteza i biološka ispitivanja

undergraduate thesis

• Title (english): Mono- and bis-1,2,3-triazolyl derivatives of benzimidazo[1,2-a]quinolines: synthesis and biological evaluations
• Author: Silvio Jakopec
• Mentor: Silvana Raić-Malić (mentor)
• Committee member: Silvana Raić-Malić (predsjednik povjerenstva)
• Committee member: Marijana Hranjec (član povjerenstva)
• Committee member: Svjetlana Krištafor (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2018-09-17, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry; Organic Chemistry

Abstract

Benzimidazo[1,2-a]kinolini su tetraciklički heteroaromatski spojevi s izraženom biološkom aktivnošću. U ovom radu priređeni su njihovi novi mono- i bis-1,2,3-triazolilni derivati i ispitana je njihova antitumorska aktivnost. Prekursor 5 za sintezu azida priređen je sintezom u tri stupnja. Azidi 6 i 7 izolirani su kao smjesa te su takvi korišteni za sintezu ciljanih spojeva Huisgenovom 1,3-dipolarnom cikloadicijom s raznim alkinima (8–13). Reakcije su provedene prema načelima click kemije, korištenjem bakrovog acetata monohidrata u metanolu pri čemu su izolirani 1,2,3-triazolilni derivati benzimidazo[1,2-a]kinolina (14–25). Strukture priređenih spojeva potvrđene su 1H i 13C NMR spektroskopijom. Biološka aktivnost ispitana je na staničnim linijama karcinoma debelog crijeva (HCT116), karcinoma dojke (MCF-7) i karcinoma pluća (H460). Mono-1,2,3-triazolilni derivati pokazali su izraženiju antitumorsku aktivnost od odgovarajućih bis-1,2,3-triazolnih analoga. Derivati benzimidazo[1,2-a]kinolina 18 i 19 koji sadrže 3-klorpropilni i 2-hidroksietilni lanac na triazolu pokazuju antiproliferativnu aktivnost u nanomolarnim koncentracijama.

Abstract (english)

Benzimidazo[1,2-a]quinolines are tetracyclic heteroaromatic compounds with pronounced biological activity. In this work, their new mono- and bis-1,2,3-triazolyl derivatives are prepared and their antitumor activity was evaluated. Precursor 5 for the azide synthesis was prepared by three-step synthesis. Azides 6 and 7 were isolated as mixture and they were used for the synthesis of target compounds by Huisgen's 1,3-dipolar cycloaddition with various alkynes (8–13). The reaction was carried out according to the principles of click chemistry, using copper acetate monohydrate in methanol, whereby 1,2,3-triazolyl derivatives of benzimidazo[1,2-a]quinoline (14–25) were isolated. The structures of the prepared compounds were confirmed by the 1H and 13C NMR spectroscopy. Biological activity was evaluated on colon cancer (HCT116), breast cancer (MCF-7) and lung cancer (H460) cell lines. Mono-1,2,3-triazolyl derivatives showed more pronounced antitumor activity compared to corresponding bis-1,2,3-triazolyl analogs. Benzimidazo[1,2-a]quinoline derivatives 18 and 19 with chloropropyl and hydroxyethyl side-chain at 1,2,3-triazole ring exhibit antiproliferative activity at nanomolar concentrations.

• Keywords: benzimidazo[1 2-a]kinolin; click kemija; bakrom(I) katalizirana azid-alkin cikloadicija; 1 2 3-triazol
• Keywords (english): benzimidazo[1 2-a]quinoline; click chemistry; copper(i)-catalyzed azide-alkyne cycloaddition; 1 2 3-triazole
• Language: croatian
• URN:NBN: urn:nbn:hr:149:556735
• Project: Number: IP-2013-11-5596; Title: Sinteza i citostatska ispitivanja biblioteke novih dušikovih heterocikla; Title: Synthesis and cytostatic evaluations of novel nitrogen heterocycles library; Acronym: SCIENcENTRY; Leader: Silvana Raić-Malić; Jurisdiction: Croatia; Funder: HRZZ; Funding stream: IP
• Study programme: Title: Applied Chemistry - Undergraduate 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: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) primijenjene kemije (sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) primijenjene kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-05-17 11:09:04