Molecular Docking and Anticonvulsant Activity of Newly Synthesized Quinazoline Derivatives
Abstract
:1. Introduction
2. Results and Discussion
2.1. Anticonvulsant Activity
2.2. Molecular Docking
3. Materials and Methods
3.1. Animals
3.2. Drugs and Chemicals
3.3. Methods
3.3.1. Subcutaneous Pentylenetetrazol (scPTZ) Screen
3.3.2. Maximal Electroshock Seizure (MES) Screen
3.3.3. Neurotoxicity
3.4. Molecular Docking
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Sample Availability: Samples of the compounds 1–24 are available from the authors. |
Compounds | R | R1 | R2 |
---|---|---|---|
1 | methyl | benzyl | - |
2 | methoxy | benzyl | - |
3 | methyl | butyl | - |
4 | methyl | butyl | ethyl |
5 | methyl | butyl | allyl |
6 | methyl | butyl | 2-Me-benzyl |
7 | methyl | butyl | 3-Me-benzyl |
8 | methyl | butyl | 4-Cl-benzyl |
9 | methyl | butyl | 4-NO2-benzyl |
10 | methyl | butyl | 2-CN-benzyl |
11 | methyl | butyl | 3-CN-benzyl |
12 | methyl | butyl | 4-CN-benzyl |
13 | methyl | butyl | 3-methoxy-benzyl |
14 | methyl | butyl | (1H-Benzoimidazol-2-yl)methyl |
15 | methyl | butyl | morphilinoethyl |
16 | methyl | benzyl | 4-CN-benzyl |
17 | methyl | benzyl | 2-methyl-benzyl |
18 | methyl | benzyl | 4-NO2-benzyl |
19 | methyl | benzyl | 7-NO2-benzoxadiazole |
20 | methoxy | benzyl | 3-(Phthalimido-2-yl)propyl |
21 | methoxy | benzyl | morphilinoethyl |
22 | methyl | butyl | hydrazine |
23 | methyl | benzyl | hydrazine |
24 | methyl | butyl | - |
Compounds | Dose a | % Protection | Neurotoxicity b | ||
---|---|---|---|---|---|
(mg/kg) | (mmol/kg) | scPTZ | MES | ||
1 | 100 | 0.301 | 50 | Nd | 0/6 |
2 | 100 | 0.376 | 33 | Nd | 0/6 |
3 | 100 | 0.234 | 67 | Nd | 0/6 |
4 | 100 | 0.239 | 33 | Nd | 0/6 |
5 | 100 | 0.253 | 20 | Nd | 0/6 |
6 | 100 | 0.267 | 67 | Nd | 0/6 |
7 | 100 | 0.212 | 67 | Nd | 0/6 |
8 | 100 | 0.248 | 100 | 33 | 0/6 |
9 | 100 | 0.241 | 33 | Nd | 0/6 |
10 | 100 | 0.204 | 50 | Nd | 0/6 |
11 | 100 | 0.255 | 50 | Nd | 0/6 |
12 | 100 | 0.355 | 33 | Nd | 0/6 |
13 | 100 | 0.239 | 100 | 33 | 0/6 |
14 | 100 | 0.373 | 25 | Nd | 0/6 |
15 | 100 | 0.245 | 83 | Nd | 0/6 |
16 | 100 | 0.252 | 83 | Nd | 0/6 |
17 | 100 | 0.329 | 0 | Nd | 0/6 |
18 | 100 | 0.309 | 17 | Nd | 0/6 |
19 | 100 | 0.338 | 100 | 17 | 0/6 |
20 | 100 | 0.331 | 67 | Nd | 0/6 |
21 | 100 | 0.251 | 33 | Nd | 0/6 |
22 | 100 | 0.352 | 75 | Nd | 0/6 |
23 | 100 | 0.291 | 0 | Nd | 0/6 |
24 | 100 | 0.325 | 67 | Nd | 0/6 |
Phenobarbital | 30 | 0.130 | 100 | Nd | Nd |
Ethosuximide | 150 | 1.060 | 100 | Nd | Nd |
Diphenyl Hydantoin | 45 | 0.160 | - | 100 | Nd |
Within the Active Binding Site of hCA II Isomer. Quinazoline Derivatives | Free Binding Energy (kcal/mol) | H-Bonds (HBs) | Closest Interaction of Quinazoline and Active Site Residues |
---|---|---|---|
3 | −3.55 | One HB: (GLN92-Q3) | ASN67, HIS64, GLN92, ILE 91 |
5 | −3.19 | One HB: (GLN92-Q5) | HIS64, ASN62, ASN67, GLU69, GLN92 |
13 | −4.01 | Two HBs ASN62-Q13 GLN92-Q13 | ILE91, PHE131, GLU69, ASN62, LEU60, ASN67, GLN92, THR200, HIS64, PRO201 |
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Abuelizz, H.A.; Dib, R.E.; Marzouk, M.; Anouar, E.-H.; A. Maklad, Y.; N. Attia, H.; Al-Salahi, R. Molecular Docking and Anticonvulsant Activity of Newly Synthesized Quinazoline Derivatives. Molecules 2017, 22, 1094. https://doi.org/10.3390/molecules22071094
Abuelizz HA, Dib RE, Marzouk M, Anouar E-H, A. Maklad Y, N. Attia H, Al-Salahi R. Molecular Docking and Anticonvulsant Activity of Newly Synthesized Quinazoline Derivatives. Molecules. 2017; 22(7):1094. https://doi.org/10.3390/molecules22071094
Chicago/Turabian StyleAbuelizz, Hatem A., Rabab El Dib, Mohamed Marzouk, El-Hassane Anouar, Yousreya A. Maklad, Hanan N. Attia, and Rashad Al-Salahi. 2017. "Molecular Docking and Anticonvulsant Activity of Newly Synthesized Quinazoline Derivatives" Molecules 22, no. 7: 1094. https://doi.org/10.3390/molecules22071094