Novel spiro[indene‐1,2′‐quinazolin]‐4′(3′H)‐one derivatives as potent anticonvulsant agents: One‐pot synthesis, in vivo biological evaluation, and molecular docking studies.

Mohammadi, Ali Asghar; Taheri, Salman; Shisheboran, Sanaz; Ahdenov, Reza; Mohammadi‐Khanaposhtani, Maryam; Darjani, Pedram Salehi; Masihi, Patrick Honarchian; Shakiba, Aidin; Larijani, Bagher; Mahdavi, Mohammad; Ahangar, Nematollah

A new series of spiro[indene‐1,2′‐quinazolin]‐4′(3′H)‐one derivatives 4a–m were synthesized via a one‐pot method and evaluated for anticonvulsant activities using pentylenetetrazole (PTZ) and maximal electroshock (MES)‐induced seizures. Obtained results demonstrated that these compounds have not anticonvulsant activity in PTZ test while are active in the MES test. Among the synthesized compounds, the best anticonvulsant activity was obtained with compound 4h. This compound also was not neurotoxic. Given that the title new compounds have the pharmacophore requirement for benzodiazepine (BZD) receptor agonist, the most potent compound was assayed in vivo and in silico as BZD receptor agonist. After treatment with flumazenil as a standard BZD receptor antagonist, anticonvulsant activity of compound 4h decreased. Therefore, the involvement of BZD receptors in anticonvulsant activity of this compound confirmed. Furthermore, docking study of compound 4h in the BZD‐binding site of GABAA receptor confirmed that this compound interacted with the important residues.

MOLECULAR docking; CHEMICAL synthesis; FLUMAZENIL; ANTICONVULSANTS

Journal of Biochemical & Molecular Toxicology, 2023, Vol 37, Issue 1, p1

1095-6670

Academic Journal

10.1002/jbt.23234