Design and synthesis of (+)-discodermolide-paclitaxel hybrids leading to enhanced biological activity

Amos B. Smith, Keizo Sugasawa, Onur Atasoylu, Chia-Ping H. Yang, Susan Band Horwitz

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Potential binding modes of (+)-discodermolide at the paclitaxel binding site of tubulin have been identified by computational studies based on earlier structural and SAR data. Examination of the prospective binding modes reveal that the aromatic pocket occupied by the paclitaxel side chain is unoccupied by (+)-discodermolide. Based on these findings, a small library of (+)-discodermolide-paclitaxel hybrids have been designed and synthesized. Biological evaluation reveals a two- to eight-fold increase in antiproliferative activity compared to the parent molecule using the A549 and MCF-7 cancer cell lines.

Original languageEnglish (US)
Pages (from-to)6319-6327
Number of pages9
JournalJournal of Medicinal Chemistry
Volume54
Issue number18
DOIs
StatePublished - Sep 22 2011

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Paclitaxel
MCF-7 Cells
Tubulin
Libraries
Binding Sites
Cell Line
discodermolide
Neoplasms

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Design and synthesis of (+)-discodermolide-paclitaxel hybrids leading to enhanced biological activity. / Smith, Amos B.; Sugasawa, Keizo; Atasoylu, Onur; Yang, Chia-Ping H.; Band Horwitz, Susan.

In: Journal of Medicinal Chemistry, Vol. 54, No. 18, 22.09.2011, p. 6319-6327.

Research output: Contribution to journalArticle

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