Application of plant allylpolyalkoxybenzenes in synthesis of antimitotic phenstatin analogues

作者：Titov Ilia Y; Sagamanova Irina K; Gritsenko Roman T; Karmanova Irina B; Atamanenko Olga P; Semenova Marina N^*; Semenov Victor V

来源：Bioorganic & Medicinal Chemistry Letters, 2011, 21(6): 1578-1581.

DOI：10.1016/j.bmcl.2011.01.124

• Allylpolyalkoxybenzenes
• Antimitotic agents
• Phenstatin
• Tubulin
• Sea urchin embryo

Phenstatin and its derivatives with the modified ring A have been synthesized, using plant allylpolyalkoxybenzenes as a starting material. The targeted molecules were evaluated in a phenotypic sea urchin embryo assay for antiproliferative activity. It was found that phenstatin ring A modifications yielded antimitotic compounds. The most effective myristicin derivative 7d (combretastatin A-2 analogue) was determined to be ca. 10 times more potent than phenstatin, displaying antimitotic tubulin-destabilizing activity at the same concentration range as combretastatins. In contrast to combretastatins, 7d featured the steric stability with potential for further design as anticancer agent.

• 出版日期2011-3-15