N-methylsansalvamide a peptide analogues. Potent new antitumor agents

Shouxin Liu, Wenxin Gu, Denise Lo, Xian Zhong Ding, Michael Ujiki, Thomas E. Adrian, Gerald A. Soff, Richard B Silverman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

Sansalvamide A, a cyclic depsipeptide isolated from a marine fungus of the genus Fusarium, is composed of four hydrophobic amino acids (Phe, two Leu, Val) and one hydroxy acid ((S)-2-hydroxy-4-methylpentanoic acid; O-Leu) with five stereogenic centers all having S-stereochemistry. We have recently synthesized the corresponding cyclic peptide (Gu, W.; Liu, S.; Silverman, R. B. Organic Lett. 2002, 4, 4171-4174) and found that it too has antitumor activity. N-Methylation can enhance potency and selectivity for peptides. Consequently, here we synthesize 12 different N-methylated sansalvamide A peptide analogues and show that for several different tumor cell lines three of these analogues are more potent than the natural product; in pancreatic cells, sansalvamide A shows little activity, but the N-methylsansalvamide peptides are potent cytotoxic agents.

Original languageEnglish (US)
Pages (from-to)3630-3638
Number of pages9
JournalJournal of Medicinal Chemistry
Volume48
Issue number10
DOIs
StatePublished - May 19 2005

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Fingerprint Dive into the research topics of 'N-methylsansalvamide a peptide analogues. Potent new antitumor agents'. Together they form a unique fingerprint.

Cite this