دورية أكاديمية
Design, synthesis and biological evaluation of 7-substituted 4-phenyl-6H-imidazo[1,5-a]thieno[3,2-f] [1,4]diazepines as safe anxiolytic agents
| العنوان: | Design, synthesis and biological evaluation of 7-substituted 4-phenyl-6H-imidazo[1,5-a]thieno[3,2-f] [1,4]diazepines as safe anxiolytic agents |
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| المؤلفون: | Di Capua A., Reale A., Paolino M., Chemi G., Brogi S., Cappelli A., Giorgi G., Grande F., Di Cesare Mannelli L., Ghelardini C., Matucci R., Garofalo A., Anzini M. |
| المساهمون: | Di Capua, A., Reale, A., Paolino, M., Chemi, G., Brogi, S., Cappelli, A., Giorgi, G., Grande, F., Di Cesare Mannelli, L., Ghelardini, C., Matucci, R., Garofalo, A., Anzini, M. |
| سنة النشر: | 2020 |
| المجموعة: | Università degli Studi della Basilicata: CINECA IRIS |
| مصطلحات موضوعية: | Anxiolytic agent, Benzodiazepine, CBR, Molecular modelling, Synthesi, Animal, Anti-Anxiety Agent, Anticonvulsant, Binding Site, Locomotion, Memory Disorder, Mice, Molecular Docking Simulation, Rat, Receptors, GABA-A, Drug Design |
| الوصف: | A series of 4-phenyl-6H-imidazo[1,5-a]thieno[3,2-f][1,4]diazepine-7-carboxylate esters were synthesized and tested as central benzodiazepine receptor (CBR) ligands by the ability to displace [3H]flumazenil from rat cortical membranes. All the compounds showed high affinity with IC50 values ranging from 5.19 to 16.22 nM. In particular, compounds 12b (IC50 = 8.66 nM) and 12d (IC50 = 5.19 nM) appeared as the most effective ligands being their affinity values significantly lower than that of diazepam (IC50 = 18.52 nM). Compounds 12a-f were examined in vivo for their pharmacological effects in mice and five potential benzodiazepine (BDZ) actions were thus taken into consideration: anxiolytic, anticonvulsant, anti-amnesic, hypnotic, and locomotor activities. All the new synthesized compounds were able to induce a significant antianxiety effect and, among them, compound 12f protected pentylenetetrazole (PTZ)-induced convulsions in a dose-dependent manner reaching a 40% effect at 30 mg/kg. In addition, all the compounds were able to significantly prevent the memory impairment evoked by scopolamine, while none of them was able to interfere with pentobarbital-evoked sleep and influence motor coordination. Moreover, title compounds did not affect locomotor and exploratory activity at the same time and doses at which the anti-anxiety effect was observed. Finally, molecular docking simulations were carried out in order to assess the binding mode for compounds 12a-f. The obtained results demonstrated that these compounds bind the BDZ binding site in a similar fashion to flumazenil. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/wos/WOS:000546723400013; volume:200; firstpage:112405; journal:EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY; https://hdl.handle.net/11563/162897Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85085545341 |
| DOI: | 10.1016/j.ejmech.2020.112405 |
| الإتاحة: | https://doi.org/10.1016/j.ejmech.2020.112405Test https://hdl.handle.net/11563/162897Test |
| حقوق: | info:eu-repo/semantics/restrictedAccess |
| رقم الانضمام: | edsbas.5F9589D6 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.ejmech.2020.112405 |
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