摘要
The serotonin 2A（5-HT2A） receptor has been implicated in several neurological conditions and potent 5-HT2A antagonists have therapeutic effects in the treatment of schizo phrenia and depression.In this study,a potent novel 5-HT2A inhibitor 05245768 with a Ki value of （593.89±34.10） nmol/L was discovered by integrating a set of computational approaches and experiments（protein structure prediction,pharmacophore-based virtual screening,automated molecular docking and pharmacological bioassay）.The 5-HT2A receptor showed a negatively charged bin-ding pocket.The binding mode of compound 05245768 with 5-HT2A was obtained by GOLD docking procedure,which revealed the conserved interaction between protonated nitrogen in compound 05245768 and carboxylate group of D3.32 at the active site of 5-HT2A.
The serotonin 2A（5-HT2A） receptor has been implicated in several neurological conditions and potent 5-HT2A antagonists have therapeutic effects in the treatment of schizo phrenia and depression.In this study,a potent novel 5-HT2A inhibitor 05245768 with a Ki value of （593.89±34.10） nmol/L was discovered by integrating a set of computational approaches and experiments（protein structure prediction,pharmacophore-based virtual screening,automated molecular docking and pharmacological bioassay）.The 5-HT2A receptor showed a negatively charged bin-ding pocket.The binding mode of compound 05245768 with 5-HT2A was obtained by GOLD docking procedure,which revealed the conserved interaction between protonated nitrogen in compound 05245768 and carboxylate group of D3.32 at the active site of 5-HT2A.
基金
Supported by the National High Technology Research and Development Program of China(No.2009AA02Z308)
the Major State Basic Research Development Program of China(No.2010CB912601)
the National Natural Science Foundation of China (No.20702009)
