Molecular-Docking Study of quinazolin-4(3H)-one derivatives against GABAa Receptor Signifies the Novel Approach to Epilepsy Treatment
Abstract
Nowadays, a lot of new active substances as antiepileptic agents have been developed. One of the protein targets of antiepileptic is selective GABA. Selective GABA is the regulator of CNS activity. In this research, quinazolinone derivatives were used to design the antiepileptic agent through a selective GABA activation. The potential activity of quinazolinone derivatives could be increased by substitution in position 3 of quinazolinone. Molecular docking of selective GABA activation was required to predict their antiepileptic activity. The molecular docking of quinazolinone derivatives was carried out using Autodock viva Ver.1.1.2. Twenty quinazolinone derivatives were docked into GABAa with PDB code 4cof. The interaction was evaluated based on the docking score. Diazepam was used as the reference standard for this research. Twenty quinazolinone derivatives showed the approximate docking score -7.1 to -9.3 kcal/mol. All twenty quinazolinone derivatives which value that have greater docking score compared to diazepam used as a standard compound. Derivative Q-18 had higher binding energy than other quinazolinone derivatives because it has the smallest docking score. All new quinazolinone derivatives are feasible to be synthesize and performed their in vitro evaluation.
Keywords:
quinazolinone, molecular docking, GABA, Epilepsy, DiazepamDOI
https://doi.org/10.25004/IJPSDR.2020.120521References
Shorvon S. Handbook of epilepsy treatment, 3rd Edition. Blackwell Science, MA (2010).
Guimarães J, and Ribeiro JAM. Pharmacology of antiepileptic drugs in clinical practice. The neurologist.2010; 16, 353–357
Vitaku E, Smith DT, Njardarson JT. Analysis of the Structural Diversity, Substitution Patterns, and Frequency of Nitrogen Heterocycles among U.S. FDA Approved Pharmaceuticals. J. Med. Chem. 2014; 57(24): 10257–10274.
Witt A, Bergman J. Recent Developments in the Field of Quinazoline Chemistry. Curr Org Chem. 2003: 7(7): 659-677.
Archana, Srivastava VK, Kumar A. Synthesis of newer thiadiazolyl and thiazolidinonyl quinazolin-4(3H)-ones as potential anticonvulsant agents. Eur J Med Chem. 2002; 37(11): 873-882.
Chapleo CB, Mayer M, Myer PL, Saville JF, Smith ACB, Stilling MR, Tulloch IF, Walter DS, Welbourn AP. Substituted 1,3,4-thiadiazoles with anticonvulsant activity. 1 Hydrazines. J Med Chem. 1986; 29:2273–2280.
Archana,Srivastava VK, Kumar A. Synthesis of some newer derivatives of substituted quinazolinonyl-2-oxo/thiobarbituric acid as potent anticonvulsant agents. Bioorg Med Chem. 2004; 12(5): 1257-1264.
Ergenc N, Buyuktimkin S, Capan G, Baktir G, Rollas S. Quinazolinones. 19. Communication [1]: Synthesis and Evaluation of Some CNS Depressant Properties of 3-(2-[(5-aryl-1,3,4-oxadiazole-2-yl)amino]acetamido)-2-methyl-4(3H)-quinazolinones. Pharmazie. 1991; 46(4): 290-291.
Kashaw SK, Kashaw V, Mishra P, Jain NK. Design, synthesis and potential CNS activity of some novel 1-(4-substituted-phenyl)-3-(4-oxo-2-propyl-4H-quinazolin-3-yl)-urea. ARKIVOC. 2008; (xiv): 17-26.
Bekhit AA, Khalil MA. Non-steroidal Anti-Inflammatory Agents: Synthesis of Novel Benzopyrazolyl, Benzoxazolyl and Quinazolinyl Derivatives of 4(3 H)-quinazolinones Pharmazie.1998; 53(8):539-543.
Alafeefy AM, Kadi AA, El-Azab AS, Abdel-Hamide SG, Daba MH. Synthesis, Analgesic and Anti-Inflammatory Evaluation of Some New 3H-quinazolin-4-one Derivatives. Arch Pharm (Weinheim). 2008; 341(6): 377-385.
Kumar A, Sharma S, Archana A, Bajaj K, Panwar H, Singh T, Srivastava VK. Some New 2,3,6-trisubstituted Quinazolinones as Potent Anti-Inflammatory, Analgesic and COX-II Inhibitors. Bioorg Med Chem. 2003; 11(23):5293-5299.
Alagarsamy V, Solomon VR, Dhanabal K. Synthesis and Pharmacological Evaluation of Some 3-phenyl-2-substituted-3H-quinazolin-4-one as Analgesic, Anti-Inflammatory Agents. Bioorg Med Chem. 2007; 15(1): 235-241.
Aziza MA, Ibrahim MK, El-Helpy AG, Al-Azhar. Design, synthesis and antiviral activity of novel quinazolinones. J. Pharm. Sci. 1994; 14: 193-201.
Al-Omary FA, Abou-Zeid LA, Nagi MN, El-Habib SE, AbdelAziz AA, El-Azab AS, Abdel-Hamide SG, Al-Omar MA, AlObaid AM, El-Subbagh HI. Non-classical Antifolates. Part 2: Synthesis, Biological Evaluation, and Molecular Modeling Study of Some New 2,6-substituted-quinazolin-4-ones. Bioorg Med Chem. 2010; 18(8): 2849-2863.
Al-Obaid AM, Abdel-Hamide SG, El-Kashef HA, Abdel-Aziz AA, El-Azab AS, Al-Khamees HA, El-Subbagh HI. Substituted Quinazolines, Part 3. Synthesis, in Vitro Antitumor Activity and Molecular Modeling Study of Certain 2-thieno-4(3H)-quinazolinone Analogs. Eur J Med Chem. 2009; 44(6): 2379-2391.
El-Azab AS, Al-Omar MA, Abdel-Aziz AA, Abdel-Aziz NI, ElSayed MA, Aleisa AM, Sayed-Ahmed MM, Abdel-Hamid SG. Design, Synthesis and Biological Evaluation of Novel Quinazoline Derivatives as Potential Antitumor Agents: Molecular Docking Study. Eur J Med Chem. 2010; 45(9): 4188-4198.
Al-Omar MA, Abdel-Hamide SG, Al-Khamees HA, El-Subbagh H. Synthesis and Biological Screening of Some New Substituted-3H-Quinazolin-4-one Analogs as Antimicrobial Agents. Saudi. Pharm. J. 2004; 12(2): 63-71.
Georgey H, Abdel-Gawad N and Abbas S. Synthesis and Anticonvulsant Activity of Some Quinazolin-4(3H)-one Derivatives. Molecules. 2008; 13: 2557-2569.
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