Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 
  • Users Online: 320
  • Home
  • Print this page
  • Email this page
ORIGINAL ARTICLE
Year : 2019  |  Volume : 14  |  Issue : 6  |  Page : 534-543

Synthesis, molecular docking, and antiepileptic activity of novel phthalimide derivatives bearing amino acid conjugated anilines


1 Department of Medicinal Chemistry, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, I.R. Iran
2 Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran; School of Pharmacy, Alborz University of Medical Sciences, Karaj, I.R. Iran
3 Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, I.R. Iran
4 Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, I.R. Iran
5 Department of Medicinal Chemistry, Faculty of Pharmacy; Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS); Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, I.R. Iran

Correspondence Address:
Massoud Amanlou
Department of Medicinal Chemistry, Faculty of Pharmacy; Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS); Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran
I.R. Iran
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1735-5362.272562

Rights and Permissions

A series of N-aryl-2-(1,3-dioxoisoindolin-2-yl)-3-phenylpropanamides derivatives were synthesized in two steps. Phthalic anhydride and phenylalanine are first reacted under microwave radiation to form 2-(1,3-dioxoisoindolin-2-yl)-3-phenylpropanoic acid, which finally took part in an amidation reaction with different anilines. The final products were characterized by infrared, proton nuclear magnetic resonance (1H NMR) and mass spectroscopy techniques. The antiepileptic activity of the synthesized compounds at a fixed dose of 10 mg/kg was evaluated by pentylenetetrazole at 70 mg/kg induced seizure threshold method in male mice (n = 5) and compared with aqueous DMSO (10 %, v/v; as negative control) and thalidomide (70 mg/kg; as positive control). The results indicated that compounds 5c, 5e, and 5f as well as thalidomide significantly have higher latency time than what observed with aqueous DMSO (P < 0.05). The seizure latency threshold for 5e and 5f were statistically similar to the results of thalidomide but compound 5c showed significantly higher latency time than thalidomide. While, the electron-deficient benzene ring (5a and 5b) has demonstrated the lowest activity but compound 5e, which is the most electron rich product among tested compounds, showed good antiepileptic activity. Molecular docking was performed in order to understand how the synthetized compounds, interact with gamma-aminobutyric acid (GABA)A receptor. Docking results were in good harmony with experimental data and indicated that lowest binding energy belongs to compound 5c, which has strongest interactions with the active site of GABAA receptor. Compound 5c could be used for further investigation.


[FULL TEXT] [PDF]*
Print this article     Email this article
 Next article
 Previous article
 Table of Contents

 Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
 Citation Manager
 Access Statistics
 Reader Comments
 Email Alert *
 Add to My List *
 * Requires registration (Free)
 

 Article Access Statistics
    Viewed336    
    Printed13    
    Emailed0    
    PDF Downloaded66    
    Comments [Add]    

Recommend this journal