GABAA Receptor Modulators with a Pyrazolo[1,5-a]quinazoline Core: Synthesis, Molecular Modelling Studies and Electrophysiological Assays

Autor: Letizia Crocetti, Gabriella Guerrini, Fabrizio Melani, Claudia Vergelli, Maria Paola Mascia, Maria Paola Giovannoni
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 23, Iss 21, p 13032 (2022)
Druh dokumentu: article
ISSN: 1422-0067
1661-6596
DOI: 10.3390/ijms232113032
Popis: As a continuation of our study in the GABAA receptor modulators field, we report the design and synthesis of new 8-chloropyrazolo[1,5-a]quinazoline derivatives. Molecular docking studies and the evaluation of the ‘Proximity Frequencies’ (exploiting our reported model) were performed on all the final compounds (3, 4, 6a–c, 7a,b, 8, 9, 12a–c, 13a,b, 14–19) to predict their profile on the α1β2γ2-GABAAR subtype. Furthermore, to verify whether the information coming from this virtual model was valid and, at the same time, to complete the study on this series, we evaluated the effects of compounds (1–100 µM) on the modulation of GABAA receptor function through electrophysiological techniques on recombinant α1β2γ2L-GABAA receptors expressed in Xenopus laevis oocytes. The matching between the virtual prediction and the electrophysiological tests makes our model a useful tool for the study of GABAA receptor modulators.
Databáze: Directory of Open Access Journals
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