Novel imidazo[4,5-b]pyridine and triaza-benzo[c]fluorene derivatives: Synthesis, antiproliferative activity and DNA binding studies

In the present paper, we have described the synthesis and biological activity of the novel derivatives of imidazo[4,5-b]pyridines and triaza-benzo[c]fluorenes (7–21, 24–26, 28–29). A preponderance of these compounds exerted strong cytostatic effects on the panel of seven human tumour cell lines in a dose-dependent manner. In particular, imidazo[4,5-b]pyridines and triaza-benzo[c]fluorenes including 2-imidazolinyl derivatives showed the most potent antitumour activity. Similarly, triaza-benzo[c]fluorenes 18 and 20 induced strong growth inhibition of tested tumour cell lines, and showed low cytotoxicity in normal human fibroblasts. DNA interaction studies of these compounds demonstrated that N-methylated 16 and 2-imidazolinyl 28 triaza-benzo[c]fluorenes bind to DNA in an intercalative mode.

A preponderance of imidazo[4,5-b]pyridines exerted strong cytostatic effects in a dose-dependent manner. Derivatives bearing 2-imidazolinyl substituent showed the most potent antitumour activity. DNA interaction studies demonstrated that compounds 16 and 28 bind to DNA in an intercalative mode.Figure optionsDownload as PowerPoint slideHighlights
► Novel imidazo[4,5-b]pyridine and triaza-benzo[c]fluorene derivatives.
► Strong cytostatic effects on the panel of seven human tumour cell lines in a dose-dependent manner.
► Intercalation into ds DNA in direct relation with concentration depended induction of apoptosis observed in SW620 and MiaPaCa-2 cells.
► High potential of some derivatives as novel leads with anticancer potentials for further in vivo evaluation.