Improvement of both plasmepsin inhibitory activity and antimalarial activity by 2-aminoethylamino substitution

Takuya Miura, Koushi Hidaka, Tsuyoshi Uemura, Keisuke Kashimoto, Yuto Hori, Yuko Kawasaki, Adam J. Ruben, Ernesto Freire, Tooru Kimura, Yoshiaki Kiso

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

We attached 2-aminoethylamino groups to allophenylnorstatine-containing plasmepsin (Plm) inhibitors and investigated SAR of the methyl or ethyl substitutions on the amino groups. Unexpectedly, compounds 22 (KNI-10743) and 25 (KNI-10742) exhibited extremely potent Plm II inhibitory activities (K i <0.1 nM). Moreover, among our peptidomimetic Plm inhibitors, we identified the compounds with the highest antimalarial activity using a SYBR Green I-based fluorescence assay.

Original languageEnglish (US)
Pages (from-to)4836-4839
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume20
Issue number16
DOIs
StatePublished - Aug 15 2010

Keywords

  • Allophenylnorstatine
  • Antimalarial drug
  • Aspartic protease
  • Hydoxymethylcarbonyl
  • Peptidomimetics
  • Plasmepsin inhibitor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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