Glioblastoma multiforme (GBM) is the most common form of malignant primary brain tumor and is one of the most lethal cancers. Despite the academic and industrial efforts to find better treatment, the 5-year survival of GBM patients has not changed over the past 10 years and is less than 9.8%. Unfortunately, the numerous anti-GBM agents currently being evaluated in clinical trials have not offered forthcoming improvement to date. GBM is characterized by resistance to apoptosis, which is largely responsible for the low effectiveness of the classical chemotherapeutic approaches, most of which are based on apoptosis induction in cancer cells. Over the past decade, a number of cell death pathways based on alternative non-apoptotic mechanisms have been discovered. In one such development, the fungal secondary metabolite ophiobolin A (OpA) was found to have significant activity against apoptosis-resistant GBM cells through the induction of a paraptotic cell death. Paraptosis is a recently discovered form of non-apoptotic cell death, which is distinguished from apoptosis by the absence of apoptotic morphology, DNA fragmentation or caspase activation. The discovery of OpA as a paraptotic agent demonstrates for the first time the possibility of paraptosis induction in GBM cells with a small molecule and lays the foundation to explore paraptosis as an innovative strategy to combat GBM. To this end, synthetic analogs derived from OpA (available in gram quantities) have been prepared and tested <i>in vitro</i> against GBM cell lines to establish preliminary structure-activity relationships (SAR). These studies will be presented with the current poster.

Preliminary structure-activity relationship studies of a fungal metabolite ophiobolin A – promising antiglioblastoma agent

249th National Meeting (2015)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.