Molecular Docking, Synthesis and Biological Evaluation of Some Novel
2-Substituted-3-allyl-4(3H)-quinazolinone Derivatives as Anticonvulsant
Hamada S Abulkhair1, Kamal M El-Gamal1,2, Khaled El-Adl3* and Mohamed F Fadl4
1Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Nasr City 11884, Cairo, Egypt
2Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy and Pharmaceutical Industries, Delta University, Mansoura, Egypt
3Pharmaceutical Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Nasr City 11884, Cairo, Egypt
4Pharmacology and Toxicology Department, Faculty of Pharmacy, Al-Azhar University, Nasr City 11884, Cairo, Egypt
- *Corresponding Author:
- Khaled El-Adl
Assistant Professor of Pharmaceutical Chemistry
Faculty of Pharmacy, Al-Azhar University
E-mail: [email protected]
Received date: September 23, 2016; Accepted date: September 29, 2016; Published date: September 30, 2016
Citation: Abulkhair HS, El-Gamal KM, El-Adl K, Fadl MF (2016) Molecular Docking, Synthesis and Biological Evaluation of Some Novel 2-Substituted-3-allyl-4(3H)- quinazolinone Derivatives as Anticonvulsant Agents. Med Chem (Los Angeles) 6:593-603. doi:10.4172/2161-0444.1000404
Copyright: © 2016 Abulkhair HS, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
A new series of 2-substituted-3-allyl-4(3H)-quinazolinone derivatives (4a-e-8a-d) were synthesized and evaluated for their anticonvulsant activity against pentylenetetrazole (PTZ)-induced seizures and maximal electroshock test in mice and compared with the reference drugs methaqualone and sodium valproate. The neurotoxicity was assessed using rotarod test. The molecular modeling was performed for all synthesized compounds to predict their binding affinity towards GABA-A receptor as a proposed mode of their anticonvulsant activity. The data obtained from the molecular docking was strongly correlated with that obtained from the biological screening which revealed that; compounds 4c, 4b and 4d showed the highest binding affinities towards GABA-A receptor and also showed the highest anticonvulsant activities in experimental mice with relatively low neurotoxicity and low toxicity in the median lethal dose test when compared with the reference drugs. The obtained results proved that the most active compounds could be useful as a model for future design, adaptation and investigation to construct more active analogs.