Synthesis of a new class of pyrrolo[3,4-h]quinazolines with antimitotic activity

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 5 different human tumor cell lines with GI50 values reaching the low micromolar level (1.3–19.8 μM). These compounds were able to induce cell death mainly by apoptosis through a mitochondrial dependent pathway. Selected compounds showed antimitotic activity and a reduction of tubulin polymerization in a concentration-dependent manner. Moreover, they showed anti-angiogenic properties since reduced in vitro endothelial cell migration and disrupted HUVEC capillary-like tube network in Matrigel. [Display omitted] •A new series of pyrrolo[3,4-h]quinazolines was conveniently prepared.•Cellular cytotoxicity was evaluated in vitro against 5 human tumor cell lines.•Inhibition of tubulin polymerization was revealed by selected compounds.