Synthesis and biological evaluation of novel indolocarbazoles with anti-angiogenic activity

A novel series of indolocarbazoles were synthesized and their antiproliferative activity against HUVEC, LoVo, DLD-1 and ST-486 cell lines, was investigated. Those staurosporine analogs in which a substituted dimethylaminoalkoxy chain was attached to the indolic nitrogen showed interesting activity and selectivity with respect to HUVEC proliferation. The effect on capillary tube formation in 3-dimensional matrigel matrix was studied using the most active compounds. Evaluation of their in vivo anti-angiogenic activity in a murine Lewis lung cancer model was also analyzed.

A new series of indolocarbazoles related to staurosporine were synthesized and their antiproliferative and anti-angiogenic activity were evaluated. 6 and 10 were the most promising compounds.Figure optionsDownload as PowerPoint slideHighlights
► Compounds with dimethylaminoalkoxy chain attached to the imidic N were most active.
► This substitution and the indolic N-substitution, improves activity and selectivity.
► In vivo and in vitro assays, confirms 6 and 10 as promising anti-angiogenic compounds.