Modification of Panobinostat to Increase its Therapeutic Potential to Cure Multiple Myeloma

Adhikari, Sweta (2017) Modification of Panobinostat to Increase its Therapeutic Potential to Cure Multiple Myeloma. Undergraduate thesis, under the direction of Davita Watkins from Department of Chemistry and Biochemistry, University of Mississippi.

Text (Thesis) Adhikari Thesis_Final.pdf - Submitted Version Restricted to Repository staff only until 31 May 2018. Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (756kB)

Abstract

Panobinostat is a potent histone deacetylase inhibitor that can impede function of a wide range of zinc-dependent histone deacetylases. Panobinostat is the first approved histone deacetylase inhibitor for the treatment of multiple myeloma, along with other drugs such as Velcade and Dexamethasone. Simplistically, it helps to shrink or eradicate tumor growth in multiple myeloma patients. However, the treatment has severe adverse effects due to its lack of selectivity. In collaboration with Dr. Shana Stoddard (Rhodes College, Memphis TN) and Fatima Rivas (St. Jude’s Research Hospital, Memphis TN), our research aims to design a more selective model of panobinostat that binds with the human histone deacetylase 8. Model compounds were examined and docking scores were computed based on protein X-ray crystal data. Herein, panobinostat derivatives having the highest docking score are presented with a synthetic scheme for the first target derivative. The synthesis and characterization by nuclear magnetic resonance (NMR) are described.

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