title: Virtual screening of protein kinase C inhibitors from natural product library to modulate general anaesthetic effects.
abstract: Protein kinase C (PKC) plays a key role in neurotransmission in the central nervous system, and targeting PKC domain is considered as a strategy to modulate the anaesthetic effects. In this study, we described a synthetic pipeline to perform high-throughput virtual screening against a large library of 3D structural natural products released recently in order to discover those potential PKC modulators. A total of 100 natural products with top scores were raised, from which 12 promising candidates were tested to determine their inhibitory potencies against PKC. As might be expected, the promiscuous kinase inhibitor staurosporine showed a high PKC inhibitory activity (IC50 = 64 nM), and other two tested compounds, i.e. fisetin and tetrahydropapaverine, were also highly potent with their activities at nanomolar level (IC50 = 370 and 190, respectively).
authors.affiliation: a Department of Anesthesiology , Weifang Medical University , 7166 Baotong Street (West), Weifang 261053 , P.R. China.
authors.forename: Junhui
authors.initials: J
authors.lastname: Zhao
authors.forename: Chuixian
authors.initials: C
authors.lastname: Zhou
mesh_terms: D018681:Anesthetics, General / Q000737:chemistry; D001688:Biological Products / Q000032:analysis*; D004791:Enzyme Inhibitors / Q000737:chemistry*; D005419:Flavonoids / Q000737:chemistry; D044948:Flavonols; D057166:High-Throughput Screening Assays; D007546:Isoquinolines / Q000737:chemistry; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D019311:Staurosporine / Q000737:chemistry*
chemical_list: D018681:Anesthetics, General; D001688:Biological Products; D004791:Enzyme Inhibitors; D005419:Flavonoids; D044948:Flavonols; D007546:Isoquinolines; C063395:tetrahydropapaverine; D011493:Protein Kinase C; D019311:Staurosporine; C017875:fisetin
keywords: anaesthetic; natural product; protein kinase C; rational drug discovery