Synthesis of novel, peptidic kinase inhibitors with cytostatic/cytotoxic activity

Wiktor Szymanski, Magdalena Zwolinska, Szymon Klossowski, Izabela Mlynarczuk-Bialy, Lukasz Bialy, Tadeusz Issat, Jacek Malejczyk, Ryszard Ostaszewski*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

12 Citations (Scopus)

Abstract

The utility of a novel, chemoenzymatic procedure for the stereocontrolled synthesis of small peptides is presented in the preparation and structure optimisation of dipeptides with cytostatic/cytotoxic activity. The method uses Passerini multicomponent reaction for the preparation of racemic scaffold which is then enantioselectively hydrolysed by hydrolytic enzymes. Products of these transformations are further functionalised towards title compounds. Both activity and selectivity towards tumor cells is optimised. Final compound is shown to be an inhibitor of the protein kinase signaling pathway. (C) 2014 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)1773-1781
Number of pages9
JournalBioorganic & Medicinal Chemistry
Volume22
Issue number5
DOIs
Publication statusPublished - 1-Mar-2014

Keywords

  • Peptidomimetics
  • Biotransformations
  • Cytostatic/cytotoxic effect
  • Kinase inhibitors
  • ALPHA-AMINO-ACIDS
  • PHASE-I
  • RAS
  • PROTEASOME
  • PATHWAY
  • GROWTH
  • CELLS

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