Jordan University of Science and Technology

Isolation, Semisynthesis, Covalent docking and Transforming Growth Factor Beta-activated Kinase 1 (TAK1)-Inhibitory Activities of (5Z)-7-Oxozeaenol analogues


Authors:  Lara Fakhouri, Tamam El-Elimat, Dow P. Hurst, Patricia H. Reggio, Cedric J. Pearce, Nicholas H. Oberlies, Mitchell P. Croatt

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.