title: A novel potential therapeutic avenue for autism: design, synthesis and pharmacophore generation of SSRIs with dual action.
abstract: Autism symptoms are currently modulated by Selective Serotonin Reuptake Inhibitors (SSRIs). SSRIs slow onset of action limits their efficiency. The established synergistic activity of SSRIs and 5HT(1B/1D) autoreceptors antagonists motivated us to incorporate SSRIs and 5HT(1B/1D) antagonists in one 'hybrid' molecule. A library of virtual 'hybrid' molecules was designed using the tethering technique. A pharmacophore model was generated derived from 16 structurally diverse SSRIs (K(i)=0.013-5000 nM) and used as 3D query. Compounds with fit values (≥2) were chosen for synthesis and subsequent in vitro biological evaluation. Our pharmacophore model is a promising milestone to a class of SSRIs with dual action.
authors: College of Pharmacy, Qatar University, PO Box 2713, Doha, Qatar. oghoneim@sjc.edu
authors: Ola M
authors: OM
authors: Ghoneim
authors: Diaa A
authors: DA
authors: Ibrahim
authors: Ibrahim M
authors: IM
authors: El-Deeb
authors: So Ha
authors: SH
authors: Lee
authors: Raymond G
authors: RG
authors: Booth
mesh_terms: D001321:Autistic Disorder / Q000188:drug therapy*; D002460:Cell Line; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D011985:Receptors, Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; D054852:Small Molecule Libraries; C078730:serotonin 5 receptor