The effect of novel negative allosteric 2,3-benzodiazepine on glutamate AMPA receptor and their cytotoxicity

2,3-Benzodiazepine (2,3-BDZ) compounds represent a group of structurally varied antagonists of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor. AMPA receptor antagonists are required to treat AMPA receptor anomalies associated with neurological illnesses, including epilepsy and stroke. Five new 2,3-BDZ compounds were tested on AMPA receptors using patch-clamp electrophysiology, while cancer cells (i.e., Hep3B, HepG2, Hela, and MCF-7) were examined using the MTS assay. Our findings indicated that adding an electron-withdrawing group (i.e., Cl or Br) inhibited AMPA receptors the most in reducing AMPA receptor cell currents and affecting the kinetics of AMPA receptors (i.e., desensitization and deactivation). Moreover, the phenyl ring of 2,3-benzodiazepine is critical for AMPA receptor binding to the affected compounds. In addition, 4b and 4e showed a potential cytotoxicity effect against Hep3B, HepG2, Hela, and MCF-7, especially Hep3B. 2,3-benzodiazepine derivatives showed neuroprotection against AMPA receptors and cytotoxicity that may be employed in several applications.