In silico search for multi-target anti-inflammatories in Chinese herbs and formulas.

Article Details

Citation
Copy to clipboard

Ehrman TM, Barlow DJ, Hylands PJ

In silico search for multi-target anti-inflammatories in Chinese herbs and formulas.

Bioorg Med Chem. 2010 Mar 15;18(6):2204-18. doi: 10.1016/j.bmc.2010.01.070. Epub 2010 Feb 8.

PubMed ID
20188577 [ View in PubMed
]
Abstract

Chinese herbs were screened for compounds which may be active against four targets involved in inflammation, using pharmacophore-assisted docking. Multiple LigandScout (LS) pharmacophores built from ligand-receptor complexes in the protein databank (PDB) were first employed to select compounds. These compounds were then docked using LS-derived templates and ranked according to docking score. The targets comprised cyclo-oxygenases 1 & 2 (COX), p38 MAP kinase (p38), c-Jun terminal-NH(2) kinase (JNK) and type 4 cAMP-specific phosphodiesterase (PDE4). The results revealed that multi-target inhibitors are likely to be relatively common in Chinese herbs. Details of their distribution are given, in addition to experimental evidence supporting these results. Examples of compounds predicted to be active against at least three targets are presented, and their features outlined. The distribution of herbs containing predicted inhibitors was also analysed in relation to 192 Chinese formulas from over 50 herbal categories. Among those found to contain a high proportion of these herbs were formulas traditionally used to treat fever, headache, rheumatoid arthritis, inflammatory bowel disorders, skin disease, cancer, and traumatic injury. Relationships between multi-target drug discovery and Chinese medicine are discussed.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
(R)-RolipramcAMP-specific 3',5'-cyclic phosphodiesterase 4DIC 50 (nM)550N/AN/ADetails
3-(Benzyloxy)Pyridin-2-AmineMitogen-activated protein kinase 14IC 50 (nM)100000N/AN/ADetails
4-(4-FLUOROPHENYL)-1-CYCLOROPROPYLMETHYL-5-(4-PYRIDYL)-IMIDAZOLEMitogen-activated protein kinase 14IC 50 (nM)160N/AN/ADetails
4-(Fluorophenyl)-1-Cyclopropylmethyl-5-(2-Amino-4-Pyrimidinyl)ImidazoleMitogen-activated protein kinase 14IC 50 (nM)25N/AN/ADetails
DaxalipramcAMP-specific 3',5'-cyclic phosphodiesterase 4BIC 50 (nM)420N/AN/ADetails
PiclamilastcAMP-specific 3',5'-cyclic phosphodiesterase 4BIC 50 (nM)0.041N/AN/ADetails
PiclamilastcAMP-specific 3',5'-cyclic phosphodiesterase 4DIC 50 (nM)0.021N/AN/ADetails
SB220025Mitogen-activated protein kinase 14IC 50 (nM)19N/AN/ADetails
ZardaverinecAMP-specific 3',5'-cyclic phosphodiesterase 4DIC 50 (nM)390N/AN/ADetails