Synthesis of new pyrrolo-, and pyrido-anellated quinazolinones as potential antiproliferative agents

Abstract

Some pyrrolo[3,2-f]quinazolinones (compounds 4–12), two pyrido[3,2-f]- and two pyrido[2,3-g]quinazolinones (compounds 15, 16 and 22, 23, respectively) were prepared via multistep syntheses. The tricyclic pyrroloquinazolinone nucleus was built starting from 5-aminoindole via a modified reported pathway to form the pyrimidine ring. To synthesize the tricyclic pyridoquinazolinones, new pathways were designed: the angular moiety was obtained starting from 6-aminoquinazolinone to form the pyridine ring and the linear one starting from the 6-aminoquinolinone to form the pyrimidine ring. An interesting antiproliferative activity was found for compound 23, which was able to form a molecular intercalative complex with DNA and to interfere with the relaxation activity of both topoisomerase I and II. The activation of the apoptotic pathway was also demonstrated.