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Synthesis of indolo[3,2-c]quinolines and indolo[3,2-d]benzazepines and their interaction with DNA

1988; Elsevier BV; Volume: 23; Issue: 2 Linguagem: Inglês

10.1016/0223-5234(88)90192-4

1768-3254

El-Sayed Ibrahim, ANITA M. MONTGOMERIE, A. Sneddon, George R. Proctor, Brian Green,

Synthesis and Biological Evaluation

A number of indolo[3,2-c]quinolines and tetrahydroindolo[3,2-d]-1-benzazepines were synthesised by Fischer indolisation of ketones including 7-chloro-1,2,3,4-tetrahydroquinol-4-one and 8-chloro-2,3,4,5-tetrahydro-1-benzazepin-5-one with several hydrazines. Some of the planar indolo[3,2-c]quinoline derivatives were shown by their effects on DNA supercoiling to form intercalation complexes with DNA and to inhibit the synthesis of macromolecules in cultured KB cells. Non-planar tetrahydroindolo[3,2-d]-1-benzazepines did not form intercalation complexes with DNA under the same conditions. 3a, b, d inhibited the synthesis of macromolecules in cultured KB cells, 3a being the most effective. No significant anti-tumor activity was detected for 3a, b, 4a, e in the NIH screening program. Des indolo[3,2-c]quinoléines et des tétrahydroindolo[3,2-d]-1-benzazépines ont été synthétisées par l'indolisation de Fischer de cétones (par exemple, chloro-7 tétrahydro-1,2,3,4 quinolone-4 et chloro-8 tétrahydro-2,3,4,5 benz-1 azépinone-5) avec des hydrazines. Les effets des dérivés plans sur le «supercoilingå de l'ADN (SV 40) laissent supposer que ces molécules s'intercalent entre les paires de bases de l'ADN. Les dérivés 3a, b, d inhibent la synthèse des macromolécules dans les cellules KB en culture, 3aétant le plus efficace. Aucun des dérivés 3a, b, 4a, e n'a manifesté une activité anti-tumorale significative.