Synthesis of benzimidazo[1,2-a]quinolines-6-carbonitrile derivatives with potential cytostatic activity

Cilj ovog rada bila je sinteza derivata benzimidazo[1,2-a]kinolin-6-karbonitrila (4-7) kao spojeva s potencijalnim antitumorskim djelovanjem. U tu svrhu iz 5-klor-2-fluorbenzimidazo[1,2-a]kinolin-6-karbonitrila (1) sintetizirani su azidi benzimidazo[1,2-a]kinolin-6-karbonitrila (2, 3). 1,2,3-triazolni derivati benzimidazo[1,2-a]kinolina (4–7) pripravljeni su reakcijom 1,3-dipolarne cikoladicije odgovarajućeg azida (2, 3) i različitih terminalnih alkina uz bakar(I) kao katalizator, prema načelima „klik“ kemije. Produkti reakcija su izolirani kolonskom kromatografijom. Strukture svih sintetiziranih spojeva potvrđene su 1H i 13C NMR spektroskopijom. Benzimidazo[1,2-a]kinolin-6-karbonitril koji sadrži 4-ciklopropil-1,2,3-triazolne supstituente u položajima 2 i 5 pokazao je snažno inhibitorno djelovanje na stanice karcinoma debelog crijeva HCT116 (GI50 = 1,6 µM).The aim of this work was the synthesis of novel benzimidazo[1,2-a]quinoline-6-carbonitrile with a potential antitumor activity. For this purpose, 5-chloro-2-fluorobenzimidazo[1,2-a]quinoline-6-carbonitrile (1) were converted to the corresponding azido derivatives of benzimidazo[1,2-a]quinoline (2, 3). 1,2,3-Triazole derivatives of benzimidazo[1,2-a]quinoline (4-7) were prepared using the reaction of 1,3-dipolar cycloaddition of the corresponding azide derivatives (2, 3) and terminal alkynes with Cu(I) as a catalyst, following the concept of “click“ chemistry. Reaction products were isolated by the column chromatography. The structures of all compounds have been confirmed by 1H i 13C NMR spectroscopy. Benzimidazo[1,2-a]quinoline-6-carbonitrile with 4-cyclopropyl-1,2,3-triazole substituents at 2 and 5 positions exhibited strong inhibitory activity against colon carcinoma HCT116 cell line (GI50 = 1,6 µM)