New pyranoquinoline derivatives as vascular-disrupting anticancer agents

Abstract

A series of new 4-aryl-pyranoquinoline derivatives with a focus on meta-nitro and meta-halophenyl derivatives were prepared and investigated for their structure-dependent antiproliferative effects on a panel of six human cancer cell lines. The compounds were highly active with nanomolar IC50 values. Some of them even exceeded the activities of known analogs such as LY290181 in vitro while not affecting non-malignant fibroblasts. These most active derivatives led to an increase of reactive oxygen species in cancer cells and to a disruption of their microtubular cytoskeleton by inhibiting tubulin polymerization. They also displayed vascular-disrupting activity in ovo as assessed by chorioallantoic membrane assays.