2. Academic Validation
  3. Design, synthesis, pharmacological evaluation, and docking study of new acridone-based 1,2,4-oxadiazoles as potential anticonvulsant agents

Design, synthesis, pharmacological evaluation, and docking study of new acridone-based 1,2,4-oxadiazoles as potential anticonvulsant agents

  • Eur J Med Chem. 2016 Apr 13:112:91-98. doi: 10.1016/j.ejmech.2016.01.054.
Maryam Mohammadi-Khanaposhtani 1,  Mohammad Shabani 2,  Mehrdad Faizi 3,  Iraj Aghaei 4,  Reza Jahani 3,  Zainab Sharafi 5,  Narges Shamsaei Zafarghandi 1,  Mohammad Mahdavi 1,  Tahmineh Akbarzadeh 6,  Saeed Emami 7,  Abbas Shafiee 1,  Alireza Foroumadi 8
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
  • 2 Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
  • 3 Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • 4 Social Determinants of Health Research Center, Guilan University of Medical Sciences, Rasht, Iran.
  • 5 Department of Pharmaceutical Biotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • 6 Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran; Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran.
  • 7 Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
  • 8 Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran; Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: aforoumadi@yahoo.com.
PMID: 26890115 DOI: 10.1016/j.ejmech.2016.01.054
Abstract

A number of acridone-based oxadiazoles 11a-n have been synthesized and evaluated for their anticonvulsant activity against pentylenetetrazole (PTZ)- and maximal electroshock (MES)-induced seizures in mice. Also, their neurotoxicity was evaluated by the rotarod test. Most of the compounds exhibited better anticonvulsant activity and higher safety respect to the standard drug, phenobarbital. Among the tested derivatives, compounds 11l with ED50 value of 2.08 mg/kg was the most potent compound in the PTZ test. The anticonvulsant effect of compound 11l was blocked by flumazenil, suggesting the involvement of benzodiazepine (BZD) receptors in the anticonvulsant activity of prototype compound 11l. Also, docking study of compound 11l in the BZD-binding site of GABAA receptor confirms possible binding of compound 11l with BZD receptors.

Keywords

1,2,4-Oxadiazole; Acridone; Anticonvulsant agents; Benzodiazepine (BZD) receptors; Docking study.

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