Synthesis and antimitotic/cytotoxic activity of hemiasterlin analogues

J Nat Prod. 2003 Feb;66(2):183-99. doi: 10.1021/np020375t.


The antimitotic sponge tripeptide hemiasterlin (1) and a number of structural analogues have been synthesized and evaluated in cell-based assays for both cytotoxic and antimitotic activity in order to explore the SAR for this promising anticancer drug lead. One synthetic analogue, SPA110 (8), showed more potent in vitro cytotoxicty and antimitotic activity than the natural product hemiasterlin (1), and consequently it has been subjected to thorough preclinical evaluation and targeted for clinical evaluation. The details of the synthesis of hemiasterlin (1) and the analogues and a discussion of how their biological activities vary with their structures are presented in this paper.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Combinatorial Chemistry Techniques*
  • Drug Screening Assays, Antitumor
  • Molecular Structure
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology
  • Porifera / chemistry*
  • Stereoisomerism
  • Structure-Activity Relationship


  • Antineoplastic Agents
  • Oligopeptides
  • hemiasterlin A