In the Ghosh Research Labs, our graduate students and post-doctoral associates are utilizing the power of organic synthesis to address many challenging problems in today's medicine. Our research spans the areas of drug design and medicinal chemistry, natural product total synthesis, organometallic chemistry and new reaction development, to tackle diverse biological problems. We are located in the R. B. Wetherill Laboratory of Chemistry, a National Historic Chemical Landmark, on the Purdue University campus.
In 2006, Darunvir received accelerated approval for HIV/AIDS patients harboring multidrug-resistant HIV-1 variants. In 2008, darunavir received full approval for both treatment-naive and treatment-experienced HIV/AIDS patients. Darunavir is currently approved in over 80 countries and is used as first-line therapy. Our recently developed protease inhibitor GRL-142 is showing exceptional properties.
We are exploring chemistry and biology of natural products. We have synthesized numerous rare and medicinally important natural products covering several dozen structural families. Our in-depth biological studies led to the discovery of new and exciting targets for anticancer drug development. These include laulimalide and peloruside as novel microtubule stabilizing agents, Lasonalide as RAFI kinase activator and spliceostatin, pladienolide and herboxidiene as novel spliceosome inhibitors.
BACE1 (β-secretase, memapsin 2) is a promising drug-development target for Alzheimer’s Disease. Since its identification in 2000, our labs pioneered the structure-based design of BACE inhibitors. We developed tools and strategies for molecular design and created many early inhibitors covering different structural classes. Inhibitor drug GRL-8234 rescues cognitive decline in transgenic mouse models for Alzheimer's disease. Several BACE inhibitors from pharma labs are in advanced clinical trials.
"Enantioselective Synthesis of Thailanstatin A Methyl Ester and Evaluation of in Vitro Splicing Inhibition" A. K. Ghosh, A. M. Veitschegger, S. Nie, N. Relitti, A. J. MacRae, M. S. Jurica. J. Org. Chem. 2018, 83, 5187-5198.
"Design of Highly Potent, Dual Acting and Central Nervous System Penetrating HIV-1 Protease Inhibitors with Excellent Potency against Multidrug-Resistant HIV-1 Variants” A. K. Ghosh; K. V. Rao, P. R. Nyalapatla, S. Kovela, M. Brindisi, H. L. Osswald, B. S. Reddy, J. Agniswamy, Y.-F. Wang, M. Aoki, S.-i. Hattori, I. T. Weber, H. Mitsuya, ChemMedChem 2018, 13, 803-815.
"Design and Development of Highly Potent HIV-1 Protease Inhibitors with a Crown-like Oxotricyclic Core as the P2-Ligand to Combat Multidrug-Resistant HIV Variants" A. K. Ghosh, K. V. Rao, P. R. Nyalapatla, H. L. Osswald, C. D. Martyr, M. Aoki, H. Hayashi, J. Agniswamy, Y.-F. Wang, H. Bulut, D. Das, I. T. Weber, H. Mitsuya J. Med. Chem. 2017, 60, 4267-4278.
"Enantioselective total synthesis and structural assignment of callyspongiolide” A. K. Ghosh, L. A. Kassekert, J. D. Bungard Org. and Biomol. Chem. 2016, 14, 11357-11370.