Anticonvulsant Activity of 3-imidazolylflavanones and Their Flexible Analogs: 1-[(2-benzyloxy)phenyl]-2-(azol-1-yl)ethanones as New Lead Compounds
- Authors: Ahangar N.1, Hafezi S.2, Irannejad H.3, Emami S.3
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Affiliations:
- Department of Toxicology and Pharmacology, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences
- Student Research Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences
- Department of Medicinal Chemistry, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences
- Issue: Vol 51, No 9 (2017)
- Pages: 787-792
- Section: Article
- URL: https://journals.rcsi.science/0091-150X/article/view/244804
- DOI: https://doi.org/10.1007/s11094-017-1694-0
- ID: 244804
Cite item
Abstract
In the search for new anticonvulsants, the (arylalkyl)azole framework has been considered as a valuable scaffold. Accordingly, a series of trans-3-imidazolylflavanones (1 – 15) and their flexible analogs 1-[(2-benzyloxy)phenyl]-2-(azol-1-yl)ethanones (16 – 19) containing an (arylalkyl)azole substructure were evaluated for their anticonvulsant activities by using pentylenetetrazole (PTZ) and maximal electroshock (MES)induced seizure tests. Also, the effect of substituent on the pendant phenyl ring and the impact of structural flexibility were investigated. The obtained results revealed that 2-(azol-1-yl)ethanone derivatives 16 – 18 exhibited 50 – 100% protection against MES-induced seizures at a dose of 100 mg/kg. Particularly, compound 16 was found to be significantly active at doses of 10 and 30 mg/kg (25 and 75% protection, respectively). This compound showed full protection at a dose of 100 mg/kg. The structure – activity relationship study revealed that the dichloro substituent in the secondary phenyl ring can improve the anticonvulsant activity. Furthermore, disconnection of the C2 – C3 bond of flavanone in trans-3-imidazolylflavanones results in flexible analogs 1-[(2-benzyloxy)phenyl]-2-(azol-1-yl)ethanones with improved anticonvulsant activity. Docking study of representative compound 16 with possible targets involved in convulsions demonstrated that the GABAA receptors can be considered as the main target for anticonvulsant activity of compound 16.
About the authors
Nematollah Ahangar
Department of Toxicology and Pharmacology, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences
Email: sd_emami@yahoo.com
Iran, Islamic Republic of, Sari
Samira Hafezi
Student Research Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences
Email: sd_emami@yahoo.com
Iran, Islamic Republic of, Sari
Hamid Irannejad
Department of Medicinal Chemistry, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences
Email: sd_emami@yahoo.com
Iran, Islamic Republic of, Sari
Saeed Emami
Department of Medicinal Chemistry, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences
Author for correspondence.
Email: sd_emami@yahoo.com
Iran, Islamic Republic of, Sari