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Medicinal Chemistry Research

, Volume 26, Issue 11, pp 2967–2984 | Cite as

Quinoxalin-2(1H)-one derived AMPA-receptor antagonists: Design, synthesis, molecular docking and anticonvulsant activity

  • Abdel-Ghany A. El-Helby
  • Rezk R. A. Ayyad
  • Khaled El-Adl
  • Alaa Elwan
Original Research

Abstract

A new series of 4-acetyl-1-substituted-3,4-dihydroquinoxalin-2(1H)-ones (314) were designed and synthesized in order to evaluate their α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-receptor antagonism as a proposed mode of their anticonvulsant activity. The structure of the synthesized compounds was confirmed by elemental analysis and spectral data (infrared, 1H nuclear magnetic resonance (NMR), 13CNMR, and mass). The molecular design was performed for all synthesized compounds to predict their binding affinity towards AMPA-receptor in order to rationalize their anticonvulsant activity in a qualitative way and explain the possible interactions that might take place between the tested derivatives and AMPA receptor in comparing to compounds III and YM872 in order to obtain the anticonvulsant effect. The data obtained from the molecular modeling was strongly correlated with that obtained from the biological screening which revealed that; compounds 14 b , 14 a , and 13 b showed the highest binding affinities toward AMPA-receptor and also showed the highest anticonvulsant activities against pentylenetetrazole-induced seizures in experimental mice. The relative potencies of these compounds were 1.89, 1.83, and 1.51 respectively, in comparing to diazepam.

Keywords

Quinoxaline Molecular docking AMPA antagonists Anticonvulsant agents 

Notes

Acknowledgements

The authors extend their appreciation and thanking to Prof. Dr. Ahmed M. Mansour, Pharmacology & Toxicology Department, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt for helping in the pharmacological screening.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Pharmaceutical Chemistry Department, Faculty of PharmacyAl-Azhar UniversityCairoEgypt
  2. 2.Pharmaceutical Chemistry Department, Faculty of PharmacyDelta UniversityDakahliaEgypt

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