Combretastatin dinitrogen-substituted stilbene analogues as tubulin-binding and vascular-disrupting agents
Abstract
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
Recommended Citation
Siles, R., Ackley, J., Hadimani, M., Hall, J., Mugabe, B., Guddneppanavar, R., Monk, K., & Chapuis, J. (2008). Combretastatin dinitrogen-substituted stilbene analogues as tubulin-binding and vascular-disrupting agents. Journal of Natural Products, 71 (3), 313-320. https://doi.org/10.1021/np070377j
