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 ?1?2?2-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 ?1?2?2L-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.

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

Maria Paola Mascia;
2022

Abstract

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 ?1?2?2-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 ?1?2?2L-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.
2022
GABAA receptor modulators; electrophysiological studies; molecular modeling; pyrazolo[1
5-a]quinazoline.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14243/415794
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact