Pharmacophores generation of multiple anti-inflammatory targets and identification of active compounds in Chinese herbs

Abstract

Chinese herbs always have activity on multiple targets. For the identification of potential anti-inflammatory compounds from Chinese herbs, six targets, which are mostly associated with inflammatory, were selected as following: Cox-2 (cyclooxygenase 2), PDE4B (phosphodiesterase 4B), p38α MAPK (p38α mitogen-activated protein kinase), JNK3 (c-Jun N-terminal kinases 3), ICE (interlenkin-1β converting enzyme) and iNOS (inducible type of nitric oxide synthase). Structure-based pharmacophore models of the inhibitors of each target were generated by LigandScout based on complexes from the PDB (Protein Data Bank). Based on the screening results of MDDR (MDL Drug Data Report database) and a new metric CAI (comprehensive appraisal index), the best models for each target were defined and used to identify the potential anti-inflammatory compounds from Chinese herbs. Six compounds and sixteen herbs were obtained that can act on multiple targets. The traditional function of the most hit herbs was `heat-clearing and detoxifying', which has been experimentally demonstrated to have anti-inflammatory activity.