Fungal metabolite ophiobolin A as a promising anti-glioma agent: In vivo evaluation, structure-activity relationship and unique pyrrolylation of prima...
Basic Information
ID: ALA3621064
Journal: Bioorg Med Chem Lett
Title: Fungal metabolite ophiobolin A as a promising anti-glioma agent: In vivo evaluation, structure-activity relationship and unique pyrrolylation of primary amines.
Authors: Dasari R, Masi M, Lisy R, Ferdérin M, English LR, Cimmino A, Mathieu V, Brenner AJ, Kuhn JG, Whitten ST, Evidente A, Kiss R, Kornienko A.
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).
CiteXplore: 26341136
DOI: 10.1016/j.bmcl.2015.08.066
Patent ID: ┄