Mono- i bis-1,2,3-triazolilni derivati benzimidazo[1,2-a]kinolina: sinteza i biološka ispitivanja
| Autor: | Jakopec, Silvio |
|---|---|
| Přispěvatelé: | Raić-Malić, Silvana |
| Jazyk: | chorvatština |
| Rok vydání: | 2018 |
| Předmět: |
bakrom(I) katalizirana azid-alkin cikloadicija
benzimidazo[1 2-a]quinoline PRIRODNE ZNANOSTI. Kemija. Organska kemija NATURAL SCIENCES. Chemistry. Organic Chemistry click chemistry benzimidazo[1 2-a]kinolin copper(i)-catalyzed azide-alkyne cycloaddition 1 2 3-triazole 1 2 3-triazol benzimidazo[1 2-a]kinolin click kemija bakrom(I) katalizirana azid-alkin cikloadicija 1 2 3-triazol click kemija |
| Popis: | 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. 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. |
| Databáze: | OpenAIRE |
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