Design, synthesis and biological evaluation of dihydronaphthalene and benzosuberene analogs of the combretastatins as inhibitors of tubulin polymerization in cancer chemotherapy

作者：Sriram Madhavi; Hall John J; Grohmann Nathan C; Strecker Tracy E; Wootton Taylor; Franken Andreas; Trawick Mary Lynn; Pinney Kevin G^*

来源：Bioorganic & Medicinal Chemistry, 2008, 16(17): 8161-8171.

DOI：10.1016/j.bmc.2008.07.050

• benzosuberenes
• dihydronaphthalenes
• combretastatins
• tubulin
• vascular disrupting agents
• cancer chemotherapy

A novel series of dihydronaphthalene and benzosuberene analogs bearing structural similarity to the combretastatins in terms of 1,2-diarylethene, trimethoxyphenyl, and biaryl functionality has been synthesized. The compounds have been evaluated in regard to their ability to inhibit tubulin assembly and for their cytotoxicity against selected human cancer cell lines. From this series of compounds, benzosuberene analogs 2 and 4 inhibited tubulin assembly at concentrations comparable to that of combretastatin A-4 (CA4) and combretastatin A-1 (CA1). Furthermore, analog 4 demonstrated remarkable cytotoxicity against the three human cancer cell lines evaluated ( for example GI(50) = 0.0000032 mu M against DU-145 prostate carcinoma).

• 出版日期2008-9-1