Novel sulfonate analogues of combretastatin A-4: potent antimitotic agents

• Published in: Bioorganic & medicinal chemistry letters 2001-04, Vol.11 (7), p.871-874
• Main Authors: Gwaltney, Stephen L., Imade, Hovis M., Barr, Kenneth J., Li, Qun, Gehrke, Laura, Credo, R.Bruce, Warner, Robert B., Lee, Jang Yun, Kovar, Peter, Wang, Jieyi, Nukkala, Michael A., Zielinski, Nicolette A., Frost, David, Ng, Shi-Chung, Sham, Hing L.
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; ATP Binding Cassette Transporter, Subfamily B, Member 1 - biosynthesis; ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics; Binding Sites - physiology; Binding, Competitive; Biological and medical sciences; Cell Division - drug effects; Colchicine - antagonists & inhibitors; Colchicine - metabolism; General aspects; Humans; Medical sciences; Pharmacology. Drug treatments; Polymers - metabolism; Stilbenes - chemistry; Stilbenes - pharmacology; Tubulin - metabolism; Tubulin Modulators; Tumor Cells, Cultured - cytology; Tumor Cells, Cultured - drug effects
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(01)00098-1

Sulfonate analogues of combretastatin A-4 have been prepared. These compounds compete with colchicine and combretastatin A-4 for the colchicine binding site on tubulin and are potent inhibitors of tubulin polymerization and cell proliferation. Importantly, these compounds also inhibit the proliferation of P-glycoprotein positive (+) cancer cells, which are resistant to many other antitumor agents. Sulfonate analogues of combretastatin A-4 have been prepared. These compounds bind to the colchicine binding site on tubulin and are potent inhibitors of tubulin polymerization and cell proliferation. Importantly, these compounds also inhibit the proliferation of P-glycoprotein positive (+) cancer cells, which are resistant to many other antitumor agents.