Zhao, Peng published the artcileThe molecular basis for the inhibition of phosphodiesterase-4D by three natural resveratrol analogs. Isolation, molecular docking, molecular dynamics simulations, binding free energy, and bioassay, Recommanded Product: 5-(6-Hydroxybenzofuran-2-yl)benzene-1,3-diol, the publication is Biochimica et Biophysica Acta, Proteins and Proteomics (2013), 1834(10), 2089-2096, database is CAplus and MEDLINE.
The phosphodiesterase-4 (PDE4) enzyme is a promising therapeutic target for several diseases. Our previous studies found resveratrol and moracin M to be natural PDE4 inhibitors. In the present study, three natural resveratrol analogs [pterostilbene, (E)-2′,3,5′,5-tetrahydroxystilbene (THSB), and oxyresveratrol] are structurally related to resveratrol and moracin M, but their inhibition and mechanism against PDE4 are still unclear. A combined method consisting of mol. docking, mol. dynamics (MD) simulations, binding free energy, and bioassay was performed to better understand their inhibitory mechanism. The binding pattern of pterostilbene demonstrates that it involves hydrophobic/aromatic interactions with Phe340 and Phe372, and forms hydrogen bond(s) with His160 and Gln369 in the active site pocket. The present work also reveals that oxyresveratrol and THSB can bind to PDE4D and exhibits less neg. predicted binding free energies than pterostilbene, which was qual. validated by bioassay (IC50 = 96.6, 36.1, and 27.0 μM, resp.). Addnl., a linear correlation (R2 = 0.953) is achieved for five PDE4D/ligand complexes between the predicted binding free energies and the exptl. counterparts approx. estimated from their IC50 values (≈RT ln IC50). Our results imply that hydrophobic/aromatic forces are the primary factors in explaining the mechanism of inhibition by the three products. Results of the study help to understand the inhibitory mechanism of the three natural products, and thus help the discovery of novel PDE4 inhibitors from resveratrol, moracin M, and other natural products.
Biochimica et Biophysica Acta, Proteins and Proteomics published new progress about 56317-21-6. 56317-21-6 belongs to benzofurans, auxiliary class Metabolic Enzyme,PDE,Natural product, name is 5-(6-Hydroxybenzofuran-2-yl)benzene-1,3-diol, and the molecular formula is C6H20Cl2N4, Recommanded Product: 5-(6-Hydroxybenzofuran-2-yl)benzene-1,3-diol.
Referemce:
https://en.wikipedia.org/wiki/Benzofuran,
Benzofuran | C8H6O – PubChem