Synthesis of Antiproliferative Cephalotaxus Esters and Their Evaluation against Several Human Hematopoietic and Solid Tumor Cell Lines: Uncovering Differential Susceptibilities to Multidrug Resistance
✍ Scribed by Joseph D. Eckelbarger; Jeremy T. Wilmot; Matthew T. Epperson; Chandar S. Thakur; David Shum; Christophe Antczak; Leonid Tarassishin; Hakim Djaballah; David Y. Gin
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 566 KB
- Volume
- 14
- Category
- Article
- ISSN
- 0947-6539
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✦ Synopsis
Abstract
Deoxyharringtonine (2), homoharringtonine (3), homodeoxyharringtonine (4), and anhydroharringtonine (5) are reported to be among the most potent members of the antileukemia alkaloids isolated from the Cephalotaxus genus. Convergent syntheses of these four natural products are described, each involving novel synthetic methods and strategies. These syntheses enabled evaluation of several advanced natural and non‐natural compounds against an array of human hematopoietic and solid tumor cells. Potent cytotoxicity was observed in several cell lines previously not challenged with these alkaloids. Variations in the structure of the ester chain within this family of alkaloids confer differing activity profiles against vincristine‐resistant HL‐60/RV+, signalling new avenues for molecular design of these natural products to combat multi‐drug resistance.