First Total Synthesis and Structure-Activity Relationship of Iheyamide A, an Antitrypanosomal Linear Peptide Isolated from a Dapissp. Marine Cyanobacterium

Arihiro Iwasaki, Kazuya Teranuma, Naoaki Kurisawa, Yulia Rahmawati, Ghulam Jeelani, Tomoyoshi Nozaki, William H. Gerwick, Kiyotake Suenaga

Research output: Contribution to journalReview articlepeer-review

Abstract

Iheyamide A ( 1 ) is an antitrypanosomal linear peptide isolated from aDapissp. marine cyanobacterium by our group in 2020, and based on structure-activity relationships of its natural analogues, the C-terminal pyrrolinone moiety has been identified as the phamacophore for its antiparasitic activity. Further, we isolated this pyrrolinone moiety by itself as a new natural product from the marine cyanobacterium and named it iheyanone ( 2 ). As expected, iheyanone ( 2 ) showed antitrypanosomal activity, but its potency was weaker than iheyamide A ( 1 ). To clarify more detailed structure-activity relationships, we completed a total synthesis of iheyamide A ( 1 ) along with iheyanone ( 2 ) and evaluated the antitrypanosomal activities of several synthetic intermediates. As a result, we found that the longer the peptide chain, the stronger the antitrypanosomal activity. As iheyamide A ( 1 ) showed selective toxicity againstTrypanosoma brucei rhodesiense, these findings can provide design guidelines for antitrypanosomal drugs.

Original languageEnglish
Pages (from-to)2587-2593
Number of pages7
JournalJournal of Natural Products
Volume84
Issue number9
DOIs
Publication statusPublished - 2021 Sep 24

ASJC Scopus subject areas

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

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