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

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

  • Bioorg Med Chem. 2015 Nov 1;23(21):6993-9. doi: 10.1016/j.bmc.2015.09.037.
Lara Fakhouri 1,  Tamam El-Elimat 1,  Dow P Hurst 1,  Patricia H Reggio 1,  Cedric J Pearce 2,  Nicholas H Oberlies 1,  Mitchell P Croatt 1
Affiliations

Affiliations

  • 1 Department of Chemistry and Biochemistry, Natural Products and Drug Discovery Center, University of North Carolina at Greensboro, Greensboro, NC 27402, USA.
  • 2 Mycosynthetix, Inc., 505 Meadowlands Drive, Suite 103, Hillsborough, USA.
PMID: 26481152 DOI: 10.1016/j.bmc.2015.09.037
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.

Keywords

(5Z)-7-Oxozeaenol; Covalent docking; Resorcylic acid lactone; Selectfluor®; TAK1.

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