The paradoxical situation in which the pharmaceutical industry now finds itself, where breakthroughs in technology and an increasing volume of chemical and biological information have been matched by a puzzling decrease in the emergence of new drug entities, has led many to wonder whether a return to nature may not offer some attractions in rediscovering the ‘sweet spot’ in drug discovery.1
Yet, due in part to the relative neglect of natural products over recent decades, both the volume and quality of information necessary to evaluate fully the potential of new chemical entities, particularly in the initial stages of selection, is often less than satisfactory. This is particularly true of phytochemicals compared to natural products of microbial origin. Thus, only a single monograph exists so far which attempts to bring together data on the molecular targets of plant compounds,2 and though information on the chemical constituents of herbs has seen an almost exponential increase over recent decades, it is perhaps doubtful whether such progress can be sustained in view of the alarming rate at which species of potential medicinal value may be disappearing.3
Chinese herbs were screened by Ehrman, Barlow & Hylands (2010) 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-NH2 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.
Bioorganic & Medicinal Chemistry, Volume 18, Issue 6, 15 March 2010, Pages 2204-2218
1.Rollinger, J. M.; Stuppner, H.; Langer, T. Prog. Drug Res. 2008, 65, 213.
2.Polya, G. Biochemical Targets of Plant Bioactive Compounds: A Pharmacological Reference Guide to Sites of Action and Biological Effects; Taylor & Francis: London, 2003.
3.Hawkins, B. Plants for Life: Medicinal Plant Conservation and Botanic Gardens; Botanic Gardens Conservation International: Richmond, UK, 2008. p 6