Isolation, Semisynthesis, Covalent Docking and Transforming Growth Factor Beta-Activated Kinase 1 (TAK1)-Inhibitory Activities of (5Z)-7-Oxozeaenol Analogues

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Mitchell Croatt, Assistant Professor (Creator)
Tamam M. El-Elimat (Creator)
Dow P. Hurst, Research Scientist (Creator)
Nicholas Oberlies, Patricia A. Sullivan Distinguished Professor of Chemistry (Creator)
Cedric J Pearce, Adjunct Professor (Creator)
Patricia H. Reggio, Professor and Department Head (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/

Abstract: (5Z)-7-Oxozeanol and related analogues were isolated and screened to explore their activity as TAK1 inhibitors. Seven analogues were synthesized and more than a score of natural products isolated that examined the role that different areas of the molecule contribute to TAK1 inhibition. A novel nonaromatic difluoro-derivative was synthesized that had similar potency compared to the lead. This is the first example of a nonaromatic compound in this class to have TAK1 inhibition. Covalent docking for the isolated and synthesized analogues was carried out and found a strong correlation between the observed activities and the calculated binding.

Additional Information

Publication
Bioorganic & Medicinal Chemistry, 23(21), 6993-6999
Language: English
Date: 2015
Keywords
(5Z)-7-Oxozeaenol, TAK1, Selectfluor®, Covalent docking, Resorcylic acid lactone

Email this document to