Title of article
Total synthesis and evaluation of C25-benzyloxyepothilone C for tubulin assembly and cytotoxicity against MCF-7 breast cancer cells
Author/Authors
Oliver E. Hutt، نويسنده , , Bollu S. Reddy، نويسنده , , Sajiv K. Nair، نويسنده , , Emily A. Reiff، نويسنده , , John T. Henri، نويسنده , , Jack F. Greiner، نويسنده , , Ting-Lan Chiu، نويسنده , , David G. VanderVelde، نويسنده , , Elizabeth A. Amin، نويسنده , , Richard H. Himes، نويسنده , , Gunda I. Georg، نويسنده ,
Issue Information
روزنامه با شماره پیاپی سال 2008
Pages
3
From page
4904
To page
4906
Abstract
The total synthesis of C25-benzyloxy epothilone C is described. A sequential Suzuki–Aldol–Yamaguchi macrolactonization strategy was utilized employing a novel derivatized C8–C12 fragment. The C25-benzyloxy analog exhibited significantly reduced biological activity in microtubule assembly and cytotoxicity assays. Molecular modeling simulations indicated that excessive steric bulk in the C25 position may reduce activity by disrupting key hydrogen bonds that are crucial for epothilone binding to β-tubulin.
Keywords
Epothilones , total synthesis , cytotoxicity , Tubulin assembly , C-25 epothilone analogue
Journal title
Bioorganic & Medicinal Chemistry Letters
Serial Year
2008
Journal title
Bioorganic & Medicinal Chemistry Letters
Record number
799915
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