Synthesis and evaluation of ether-linked demethylepipodophyllotoxin dimers

  • Bioorg Med Chem Lett. 2014 Dec 15;24(24):5627-5629. doi: 10.1016/j.bmcl.2014.10.082.
Norma Dunlap  1 ,  Tracy L J Salyard  1 ,  Anuradha Liyana Pathiranage  1 ,  Jeannie Stubblefield  1 ,  Steven L Pitts  2 ,  Rachel E Ashley  2 ,  Neil Osheroff  2
Affiliations
  • 1. Department of Chemistry, Middle Tennessee State University, 1301 Main St., Murfreesboro, TN, USA.
  • 2. Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.
PMID: 25466187 DOI: 10.1016/j.bmcl.2014.10.082
Abstract

A series of novel ether-linked dimers of demethylepipodophyllotoxin are Topoisomerase II poisons that exhibit higher levels of double-stranded versus single-stranded DNA cleavage than their corresponding monomers. The dimers also have higher levels of tumor cell cytotoxicity than the monomers, lending support to the two-drug model for interaction of demethylepipodophyllotoxins with human Topoisomerase IIα.

Keywords
Cytotoxicity; Demethylepipodophyllotoxin; Topoisomerase.