title: Synthesis and biological evaluation of novel flavanone derivatives as potential antipsychotic agents.
abstract: In this study, a series of novel flavanone derivatives were designed and synthesized, and the antipsychotic activities of the target compounds were evaluated in vitro and in vivo. The results showed that synthesized compounds 7a-7g decreased the activity of dopamine D2receptors in HEK293 cells co-transfected with D2receptor/G protein α16a, with IC50values of 0.051-0.35 μm. Compounds 7a-7g inhibited the over-production of nitric oxide stimulated by lipopolysaccharide/interferon-γ in BV-2 microglial cells. In mice, intragastric administration of 7d, 7e, and 7g reversed the increase in locomotor activity induced by MK-801 (an antagonist of NMDA receptors) and decreased the hyperactivity of climbing behavior induced by apomorphine (a dopamine receptor agonist). These results suggest that some of the novel flavanone derivatives have potential antipsychotic effects and may be useful in the treatment of schizophrenia.
authors.affiliation: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Beijing Institute for Brain Disorders, Beijing Engineering Research Center for Nerve System Drugs, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, China.
authors.forename: Hong-Shun
authors.initials: HS
authors.lastname: Gu
authors.affiliation: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Beijing Institute for Brain Disorders, Beijing Engineering Research Center for Nerve System Drugs, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: School of Chemical Biology and Pharmaceutical Sciences, Capital Medical University, Beijing, China.
authors.forename: Jian-Wei
authors.initials: JW
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Beijing Institute for Brain Disorders, Beijing Engineering Research Center for Nerve System Drugs, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Beijing Institute for Brain Disorders, Beijing Engineering Research Center for Nerve System Drugs, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001058:Apomorphine / Q000009:adverse effects / Q000494:pharmacology; D060326:Chemistry Techniques, Synthetic; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000009:adverse effects / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D044950:Flavanones / Q000737:chemistry*; D057809:HEK293 Cells / Q000187:drug effects; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012559:Schizophrenia / Q000139:chemically induced / Q000188:drug therapy
chemical_list: D014150:Antipsychotic Agents; D044950:Flavanones; D017448:Receptors, Dopamine D2; D009569:Nitric Oxide; D016291:Dizocilpine Maleate; D001058:Apomorphine; C028610:flavanone
keywords: MK-801; Neuroinflammation; apomorphine; dopamine D2 receptor; flavanone derivatives; schizophrenia