A new series of pyrrolo[3,4-h]quinazolines was conveniently prepared with a broad substitution pattern.A large number of derivatives was obtained and the cellular cytotoxicity was evaluated in vitro against 5different human tumor cell lines with GI50 values reaching the low micromolar level (1.3e19.8 mM).These compounds were able to induce cell death mainly by apoptosis through a mitochondrial dependentpathway. Selected compounds showed antimitotic activity and a reduction of tubulin polymerizationin a concentration-dependent manner. Moreover, they showed anti-angiogenic properties sincereduced in vitro endothelial cell migration and disrupted HUVEC capillary-like tube network in Matrigel.
- Drug Discovery
- Organic Chemistry