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

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

  • Bioorg Med Chem Lett. 2015 Oct 15;25(20):4544-8. doi: 10.1016/j.bmcl.2015.08.066.
Ramesh Dasari 1,  Marco Masi 2,  Romana Lisy 3,  Marlène Ferdérin 3,  Lance R English 1,  Alessio Cimmino 2,  Véronique Mathieu 3,  Andrew J Brenner 4,  John G Kuhn 4,  Steven T Whitten 1,  Antonio Evidente 2,  Robert Kiss 3,  Alexander Kornienko 5
Affiliations

Affiliations

  • 1 Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX 78666, USA.
  • 2 Dipartimento di Scienze Chimiche, Università di Napoli Federico II, Complesso Universitario Monte Sant'Angelo, Via Cintia 4, 80126 Napoli, Italy.
  • 3 Laboratoire de Cancérologie et de Toxicologie Expérimentale, Faculté de Pharmacie, Université Libre de Bruxelles, Brussels, Belgium.
  • 4 Cancer Therapy and Research Center, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
  • 5 Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX 78666, USA. Electronic address: a_k76@txstate.edu.
PMID: 26341136 DOI: 10.1016/j.bmcl.2015.08.066
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).

Keywords

1,4-Dicarbonyl; Paal–Knorr; Paraptosis; Pyrrole.

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