title: Synthesis and antidepressant activities of 4-(substituted-phenyl)tetrazolo[1,5-a]quinazolin-5(4H)-ones and their derivatives.
abstract: A series of novel 4-(substituted-phenyl) tetrazolo[1,5-a]quinazolin-5(4H)-ones (6a-x) and their derivatives with tetrazole and other heterocyclic substituents (7-14) were designed, synthesized, and evaluated for antidepressant activities in mice. Pharmacological tests showed that three compounds (6l, 6u, and 6v) at a dose of 50 mg/kg significantly reduced the immobility time in the forced swimming test. The most active compound was 4-(p-tolyl)tetrazolo[1,5-a]quinazolin-5(4H)-one (6v), which decreased the immobility time by 82.69 % at 50 mg/kg. Moreover, 6v did not affect spontaneous activity in the open-field test, and this effect was comparable to the antidepressant effect of fluoxetine. Noradrenaline (NE) and 5-hydroxytryptamine (5-HT) levels in the brains of mice in the test sample groups significantly increased at a dose of 50 mg/kg compared with that in the control group. The monoamine oxidase (MAO) level of all test groups was reduced, but this result was not significantly different between the groups. Therefore, we can infer that their underlying mechanisms may involve the regulation of brain monoamine neurotransmitter homeostasis, based on the detected content of NE, 5-HT, and MAO in mouse brain tissue.
authors.affiliation: Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji, 133000, People's Republic of China.
authors.forename: Hong-Jian
authors.initials: HJ
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji, 133000, People's Republic of China.
authors.forename: Shi-Ben
authors.initials: SB
authors.lastname: Wang
authors.affiliation: Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji, 133000, People's Republic of China. zsquan@ybu.edu.cn.
authors.forename: Zhe-Shan
authors.initials: ZS
authors.lastname: Quan
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D009638:Norepinephrine / Q000378:metabolism; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism; D013329:Structure-Activity Relationship; D013550:Swimming
chemical_list: D000928:Antidepressive Agents; D011799:Quinazolines; D012701:Serotonin; D009638:Norepinephrine
keywords: Antidepressant; Monoamine oxidasecontent; Noradrenaline; Open-field test; Quinazolinone