Combretastatin dinitrogen-substituted stilbene analogues as tubulin-binding and vascular-disrupting agents


Several stilbenoid compounds having structural similarity to the combretastatin group of natural products and characterized by the incorporation of two nitrogen-bearing groups (amine, nitro, serinamide) have been prepared by chemical synthesis and evaluated in terms of biochemical and biological activity. The 2′,3′-diamino B-ring analogue 17 demonstrated remarkable cytotoxicity against selected human cancer cell lines in vitro (average GI50 = 13.9 nM) and also showed good activity in regard to inhibition of tubulin assembly (IC50 = 2.8 μM). In addition, a single dose (10 mg/kg) of compound 17 caused a 40% tumor-selective blood flow shutdown in tumor-bearing SCID mice at 24 h, thus suggesting the potential value of this compound and its corresponding salt formulations as new vascular-disrupting agents. © 2008 American Chemical Society and American Society of Pharmacognosy.

Publication Title

Journal of Natural Products