Fungal metabolite ophiobolin A as a promising anti-glioma agent: In vivo evaluation, structure-activity relationship and unique pyrrolylation of primary amines

Ramesh Dasari, Marco Masi, Romana Lisy, Marlène Ferdérin, Lance R. English, Alessio Cimmino, Véronique Mathieu, Andrew Brenner, John G. Kuhn, Steven T. Whitten, Antonio Evidente, Robert Kiss, Alexander Kornienko

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Glioblastoma, the most common form of malignant primary brain tumor, is characterized by resistance to apoptosis, which is largely responsible for the low effectiveness of the classical chemotherapeutic approaches based on apoptosis induction in cancer cells. Previously, a fungal secondary metabolite ophiobolin A was found to have significant activity against apoptosis-resistant glioblastoma cells through the induction of a non-apoptotic cell death, thus, offering an innovative strategy to combat this type of cancer. The current work describes the results of a preliminary evaluation of ophiobolin A in an in vivo glioblastoma model and its chemical derivatization to establish first synthetically generated structure-activity relationship. The synthetic work has also led to the discovery of a unique reaction of ophiobolin A with primary amines suggesting the possibility of pyrrolylation of lysine residues on its intracellular target protein(s).

Original languageEnglish (US)
Pages (from-to)4544-4548
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume25
Issue number20
DOIs
StatePublished - Aug 7 2015

Keywords

  • 1 4-Dicarbonyl
  • Paal-Knorr
  • Paraptosis
  • Pyrrole

ASJC Scopus subject areas

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

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  • Cite this

    Dasari, R., Masi, M., Lisy, R., Ferdérin, M., English, L. R., Cimmino, A., Mathieu, V., Brenner, A., Kuhn, J. G., Whitten, S. T., Evidente, A., Kiss, R., & Kornienko, A. (2015). Fungal metabolite ophiobolin A as a promising anti-glioma agent: In vivo evaluation, structure-activity relationship and unique pyrrolylation of primary amines. Bioorganic and Medicinal Chemistry Letters, 25(20), 4544-4548. https://doi.org/10.1016/j.bmcl.2015.08.066