Thiazole- and imidazole-containing peptidomimetic inhibitors of protein farnesyltransferase

Cristiano Bolchi, Marco Pallavicini, Sergio K. Bernini, Giuseppe Chiodini, Alberto Corsini, Nicola Ferri, Laura Fumagalli, Valentina Straniero, Ermanno Valoti

Research output: Contribution to journalArticle

Abstract

Mimetics of the C-terminal CAAX tetrapeptide of Ras protein were designed replacing internal dipeptide AA with 4-amino-2-phenylbenzoic acid and cysteine (C) with 2-amino-4-thiazolyl-, 2-mercapto-4-thiazolyl-, 2-mercapto-4-imidazolyl- and 2-methylmercapto-4-thiazolyl-acetic or propionic acid. The compound in which C is replaced by 2-amino-4-thiazolylacetic acid inhibited FTase activity in the low nanomolar range and showed antiproliferative effect on rat aortic smooth muscle cells interfering with Ras farnesylation. On the basis of these results, 2-aminothiazole can be considered as an alternative to heterocycles, such as pyridine and imidazole, normally used in FTase inhibitors designed as non-thiol CAAX mimetics.

Original languageEnglish
Pages (from-to)5408-5412
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume21
Issue number18
DOIs
Publication statusPublished - Sep 15 2011

Keywords

  • Antiproliferative agents
  • Antitumors
  • Farnesyltransferase
  • Peptidomimetic inhibitors
  • Prenylation inihibitors

ASJC Scopus subject areas

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

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  • Cite this

    Bolchi, C., Pallavicini, M., Bernini, S. K., Chiodini, G., Corsini, A., Ferri, N., Fumagalli, L., Straniero, V., & Valoti, E. (2011). Thiazole- and imidazole-containing peptidomimetic inhibitors of protein farnesyltransferase. Bioorganic and Medicinal Chemistry Letters, 21(18), 5408-5412. https://doi.org/10.1016/j.bmcl.2011.07.003