Isolation, semisynthesis, covalent docking and transforming growth factor beta-activated kinase 1 (TAK1)-inhibitory activities of (5Z)-7-oxozeaenol analogues.

Authors :: Fakhouri L
El-Elimat T
Hurst DP
Reggio PH
Pearce CJ
Oberlies NH
Croatt MP
Source :: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2015 Nov 01; Vol. 23 (21), pp. 6993-9. Date of Electronic Publication: 2015 Sep 25.
Publication Year :: 2015
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.<br /> (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Subjects :: Binding Sites
Humans
Inhibitory Concentration 50
MAP Kinase Kinase Kinases metabolism
Molecular Docking Simulation
Protein Kinase Inhibitors chemistry
Protein Kinase Inhibitors metabolism
Protein Structure, Tertiary
Zearalenone chemical synthesis
Zearalenone chemistry
Zearalenone metabolism
MAP Kinase Kinase Kinases antagonists & inhibitors
Protein Kinase Inhibitors chemical synthesis
Zearalenone analogs & derivatives

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