The Quest for a Simple Bioactive Analog of Paclitaxel as a Potential Anticancer Agent

• Type of Material: Article
• Authors: David G.I. Kingston, Virginia Tech; James Snyder, Emory University
• Language: English
• Date: 2014-08-19
• Publisher: American Chemical Society
• Publication Version: Final Published Version
• Copyright Statement: © 2014 American Chemical Society
• Final Published Version (URL): http://dx.doi.org/10.1021/ar500203h
• Title of Journal or Parent Work: Accounts of Chemical Research
• ISSN: 0001-4842
• Volume: 47
• Issue: 8
• Start Page: 2682
• End Page: 2691
• Grant/Funding Information: National Institutes of Health, United States; We are grateful to the National Cancer Institute, Grant CA-69571 to D.G.I.K., for financial support of the work at Virginia Tech and to J.P.S. for the work at Emory University.
• Research Categories: Chemistry, General

Abstract

Paclitaxel (PTX), introduced into the clinic in 1991, has revealed itself as an effective antimicrotubule drug for treatment of a range of otherwise intractable cancers. Along with docetaxel (DTX) and in combination with other agents such as cisplatin, it has proven to be a first-line therapy. Unfortunately, PTX and DTX carry severe liabilities such as debilitating side effects, rapid onset of resistance, and rather complex molecular structures offering substantial challenges to ease of synthetic manipulation. Consequently, the past 15 years has witnessed many efforts to synthesize and test highly modified analogs based on intuitive structural similarity relationships with the PTX molecular skeleton, as well as efforts to mimic the conformational profile of the ligand observed in the macromolecular tubulin–PTX complex.