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

Nidal Jaradat*, Mohammed Hawash, Mohammad Qneibi, Tahrir Shtayeh, Shorooq Sobuh, Mohammed Arar, Sosana Bdir

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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.

Original languageAmerican English
Article number132936
JournalJournal of Molecular Structure
Volume1261
DOIs
StatePublished - 5 Aug 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2022

Keywords

  • 2,3-benzodiazepine compounds
  • AMPA receptor
  • Cytotoxicity
  • Deactivation
  • Desensitization

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