Evaluation of di-sansalvamide A derivatives: synthesis, structure-activity relationship, and mechanism of action

  • J Med Chem. 2009 Dec 24;52(24):7927-30. doi: 10.1021/jm901566c.
Leslie D Alexander  1 ,  Robert P Sellers ,  Melinda R Davis ,  Veronica C Ardi ,  Victoria A Johnson ,  Robert C Vasko ,  Shelli R McAlpine
Affiliations
  • 1. Department of Chemistry and Biochemistry, San Diego State University, San Diego, CA 92182-1030, USA.
PMID: 20014866 DOI: 10.1021/jm901566c
Abstract

Described is the SAR of 18 di-sansalvamide A derivatives and the mechanism of action of the most potent compound. We show that this scaffold is a promising lead in the development of novel Cancer therapeutics because it is cytotoxic at nanomolar potency, inhibits a well-established oncogenic target (HSP90), and does not share structural motifs with current drugs on the market.