Description
Ophiobolin A (4611-05-6) selectively inhibits the growth of cancer cells (IC50=0.4-4.3 μM) over normal cells (IC50=20.9 μM).1 Induces non-apoptotic cell death in glioblastoma cells and is active in an in vivo model.2 Covalently reacts with primary amines such as lysine side chains2 and phosphatidylethanolamine3 forming unique pyrrole adducts. Induces ER stress4, paraptosis4 and autophagy5.
Definition
ChEBI: A sesterterpenoid that is ophiobolane with a hydroxy group at position 3, oxo groups at positions 5 and 25, double bonds at positions 7-8 and 19-20, and an oxygen link between positions 14 and 18.
References
[1] DIMPLE R. BHATIA . Anticancer activity of Ophiobolin A, isolated from the endophytic fungus Bipolaris setariae[J]. Natural Product Research, 2016, 30 12: Pages 1455-1458. DOI:
10.1080/14786419.2015.1062760[2] RAMESH DASARI . Fungal metabolite ophiobolin A as a promising anti-glioma agent: In vivo evaluation, structure–activity relationship and unique pyrrolylation of primary amines[J]. Bioorganic & Medicinal Chemistry Letters, 2015, 25 20: Pages 4544-4548. DOI:
10.1016/j.bmcl.2015.08.066[3] CHRISTOPHER CHIDLEY. The anticancer natural product ophiobolin A induces cytotoxicity by covalent modification of phosphatidylethanolamine.[J]. eLife, 2016. DOI:
10.7554/elife.14601[4] IN YOUNG KIM. Ophiobolin A kills human glioblastoma cells by inducing endoplasmic reticulum stress via disruption of thiol proteostasis.[J]. Oncotarget, 2017, 8 63: 106740-106752. DOI:
10.18632/oncotarget.22537[5] C. RODOLFO. Ophiobolin A Induces Autophagy and Activates the Mitochondrial Pathway of Apoptosis in Human Melanoma Cells[J]. PLoS ONE, 2016, 11 1. DOI:
10.1371/journal.pone.0167672
