Gracilin A

Isolated from the marine sponge Spongionella gracilis and a member of the diterpene family, Gracilin A possesses a bisacetoxy tricyclic structure.1 Gracilin A is an inhibitor of cyclophilins A (CypA) and D (CypD) with IC50 values of 0.26 μM for CypD and 0.27 μM CypA, respectively. Inhibition of CypA has been shown to yield immunosuppression and inhibitors of CypD have been shown to provide neuroprotective effects.2,3  Gracilin’s novel structure and potent biological activity have prompted considerable synthetic and biological interest.CypA plays a crucial role in inflammatory pathways, making it a target protein for drugs intended to suppress the immune system like Cyclosporin A. CypD is involved in the opening of the mitochondrial permeability transition pore (mPTP). Opening of the mPTP causes mitochondrial dysfunction seen in neurodegenerative diseases such as Alzheimer’s disease. By identifying novel derivatives of Gracilin A that selectively bind with CypD, we hope to put forward drug leads for the treatment of neurodegenerative diseases without suppressing the immune system function.  Dr. Taube’s group is also interested in studying selective CypD inhibitors to determine the role CypD plays in cancer. The Baylor Undergraduate MiniPharma Team is an interdisciplinary, collaborative working group with the Design and Synthesis Team working with Prof. Romo, the Molecular Modeling Group working with Dr. Hull, and the Biological Assay team working with Prof. Taube to design, synthesize and test novel gracilin A derivatives.






(1)        Mayol, L.; Piccialli, V.; Sica, D. Gracilin A, an Unique: Nor-Diterpene Metabolite from the Marine Sponge Spongionella Gracilis. Tetrahedron Lett. 198526 (10), 1357–1360.

(2)        Abbasov, M. E.; Alvariño, R.; Chaheine, C. M.; Alonso, E.; Sánchez, J. A.; Conner, M. L.; Alfonso, A.; Jaspars, M.; Botana, L. M.; Romo, D. Simplified Immunosuppressive and Neuroprotective Agents Based on Gracilin A. Nat. Chem. 201911 (4), 342–350.

(3)        Leirós, M.; Alonso, E.; Rateb, M. E.; Houssen, W. E.; Ebel, R.; Jaspars, M.; Alfonso, A.; Botana, L. M. Gracilins: Spongionella-Derived Promising Compounds for Alzheimer Disease. Neuropharmacology 201593, 285–293.