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 J. Brenner, John G. Kuhn, Steven T. Whitten, Antonio Evidente, Robert Kiss, Alexander Kornienko

Producción científica: Articlerevisión exhaustiva

35 Citas (Scopus)

Resumen

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).

Idioma originalEnglish (US)
Páginas (desde-hasta)4544-4548
Número de páginas5
PublicaciónBioorganic and Medicinal Chemistry Letters
Volumen25
N.º20
DOI
EstadoPublished - oct 15 2015

ASJC Scopus subject areas

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

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