Antineoplastic Agents. 607. Emetine Auristatins

George R. Pettit, Noeleen Melody, Jean Charles Chapuis

Research output: Contribution to journalArticle

Abstract

The remarkable biological activity of the dolastatin 10 structural modifications quinstatins and isoquinstatins prompted further investigation into drug hybrids containing biologically active isoquinoline moieties. In this study, the isoquinoline alkaloid emetine was selected as one of the structural domains of a hybrid molecule. That was accomplished by covalently bonding the Dov-Val-Dil-Dap peptide sequence of dolastatin 10 peptide at the N-2′ secondary amine of emetine. Three new hybrids were synthesized, 5, 9, and 10. Comparison of the biological activity of these new peptide-emetine analogues with emetine showed complete retention of activity for 5 and a 10-fold decrease for hybrids 9 and 10. The result was surprising, as the activity of emetine is usually lost or greatly reduced when substituted at the N-2′ position.

Original languageEnglish (US)
Pages (from-to)1571-1576
Number of pages6
JournalJournal of Natural Products
Volume83
Issue number5
DOIs
StatePublished - May 22 2020

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

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