Antiproliferative activity of Pyrrolo[3,2-c]quinoline derivatives

The pyrrolo[3,2-c]quinoline scaffold has been known as a core structure of a wide number of bioactive molecules. Several derivatives of such a tricyclic angular heterocycle have shown a wide spectrum of biological activities, such as hypotensive, anti-inflammatory properties, gastric (H)ATPase inhibition effect, and remarkable antitumor activity (1). The high therapeutic potentiality of such a skeleton along with our interest in targets featuring aza-polycondensed aromatic structures, attracted us to develop an alternative synthetic strategy, in order to reach a series of pyrrolo[3,2-c]quinolines in quantitative yields (2). The reaction of 3-acetyl-1,4-dione 1 with selected amines allowed the isolation of intermediates 2. Subsequent reduction of the nitro group and condensation with substituted aldehydes drove the cyclization to pyrrolo[3,2-c]quinoline ring system 3.Substituted pyrrolo[3,2-c]quinolines 3 were preliminary evaluated for antiproliferative activity (MTS assays) against 5 human tumor cell lines (colon tumor Caco2; breast cancer MCF7; brain cancer LAN5; cervix HeLa and lung tumor H292), and human epithelial bronchial cell line 16HBE as control. Moreover, benzomethylen-dioxy derivative tested at DTP/NCI showed an appreciable and selective cell growth inhibitory effect against Leukemia SR, Melanoma MDA-MB-435, Renal Cancer UO-31 cell lines.