Synthesis, in vitro antitumor evaluation and DNA-binding study of novel tetrahydroquinolines and some derived tricyclic and tetracyclic ring systems

The synthesis of some new tetrahydroquinolines, tetrahydropyrimido[4,5-b]quinolines, and tetrahydropentaazacyclopenta[a]anthracenes structurally related to some DNA intercalators is described. Fifteen compounds were evaluated for their antitumor activity by the National Cancer Institute (NCI), in vitro disease oriented antitumor screening. The most active tricyclic pyrimido[4,5-b]quinolines 3b, 6b, 7b and 8b were further subjected to DNA-binding investigation in an attempt to rationalize their activity. Compound 8b proved to be the most active member in this study as evidenced from its remarkable growth inhibitory potential against some individual cell lines, and its broad spectrum of antitumor activity (GI50, TGI and LC50 values 46.9, 85.3 and 97.4, respectively), together with a good DNA-binding affinity.

Several tetrahydroquinolines (A), tetrahydropyrimido[4,5-b]quinolines (B), and tetrahydropentaazacyclopenta[a]anthracenes (C) were synthesized. Some tetrahydropyrimido[4,5-b]quinolines displayed broad spectrum antitumor and good DNA-binding activities.Figure optionsDownload as PowerPoint slideHighlights
► Synthesis of some new tetrahydroquinolines and some derived ring systems.
► In vitro antitumor evaluation.
► DNA-binding affinity testing.
►  4 compounds displayed broad spectrum of antitumor activity.
► Compound 8b is the most active antitumor and DNA-binding agent.