Synthesis, Docking and Antiepileptic Activity of New 2-((1,5-Diphenyl-1H-1,2,4-Triazol-3-yl)Thio)-N-Phenylacetamide Derivatives

被引：1
作者：
Amanlou, Arash [1 ]
Nassireslami, Ehsan [2 ,3 ]
Hosseini, Faezeh Sadat [4 ]
Dehpour, Ahmad Reza [1 ,5 ]
Rashidian, Amir [1 ,5 ]
Chamanara, Mohsen [2 ,3 ]
机构：
[1] Univ Tehran Med Sci, Expt Med Res Ctr, POB 13145-784, Tehran, Iran
[2] AJA Univ Med Sci, Sch Med, Dept Pharmacol, Tehran, Iran
[3] AJA Univ Med Sci, Toxicol Res Ctr, Tehran, Iran
[4] Univ Tehran Med Sci, Fac Pharm, Dept Med Chem, Tehran, Iran
[5] Univ Tehran Med Sci, Sch Med, Dept Pharmacol, Tehran, Iran
来源：
POLYCYCLIC AROMATIC COMPOUNDS | 2022年 / 42卷 / 09期
关键词：
Antiepileptic; seizures; molecular docking; synthesis; pentylenetetrazole; 1; 2; 4-triazole; PENTYLENETETRAZOLE-INDUCED SEIZURES; ANTICONVULSANT ACTIVITY; MODELS; INVOLVEMENT; EPILEPSY;
D O I：
10.1080/10406638.2021.1983616
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
In this work, a new series of 2-((1,5-diphenyl-1H-1,2,4-triazol-3-yl)thio)-N-phenylacetamide derivatives (9a-k) were synthesized and then evaluated for their antiepileptic activity against pentylenetetrazole (PTZ)-induced seizures in mice. The most potent synthesized compound was 3-chloro derivative, 9e, with an average latency time of 825 +/- 281 seconds (mean +/- SEM) and zero mortality. Moreover, compound 9e was more active than phenytoin (p < 0.1) but weaker than phenobarbital (p < 0.05) in the PTZ test. Further, a molecular docking study was performed to investigate the modes of interactions between the GABA(A) receptor and the synthesized compounds. Docking results indicate that all of the synthesized compounds place well into the active site of the GABA(A) receptor. In addition, compound 9e, with the highest anticonvulsant properties, demonstrates proper interactions and forms strong hydrogen bonds with key amino acid residues in the active site of the GABA(A) receptor. Additionally, it has exhibited higher binding energy in the docking study compared to phenobarbital and phenytoin as the standard antiepileptic agents.
引用
收藏
页码：6429 / 6443
页数：15
相关论文
共 50 条
[11]   Synthesis, Crystal Structure and Fungicidal Activity of 3-(((4-Cyclopropyl-5-Methyl-4H-1,2,4-Triazol-3-yl)Thio)Methyl)Benzonitrile H2O (1:1) Solvent [J].
Jin, Jian-Zhong ;
Sun, Na-Bo .
JOURNAL OF THE CHEMICAL SOCIETY OF PAKISTAN, 2013, 35 (03) :955-959
[12]   Synthesis of 3-methyl-4-(5-R-1H-1,2,4-triazol-3-yl)-1,2,5-oxadiazoles [J].
Godovikova, T. I. ;
Vorontsova, S. K. ;
Konyushkin, L. D. ;
Firgang, S. I. ;
Rakitin, O. A. .
RUSSIAN CHEMICAL BULLETIN, 2010, 59 (02) :483-485
[13]   Synthesis of 3-methyl-4-(5-R-1H-1,2,4-triazol-3-yl)-1,2,5-oxadiazoles [J].
T. I. Godovikova ;
S. K. Vorontsova ;
L. D. Konyushkin ;
S. I. Firgang ;
O. A. Rakitin .
Russian Chemical Bulletin, 2010, 59 :483-485
[14]   Synthesis, Crystal Structure and Antiproliferative Activity of 2-(((5-(((5,7-Dimethyl-[1,2,4]triazolo-[1,5-a]pyrimidin-2-yl)thio)methyl)-4-phenyl-4H-1,2,4-triazol-3-yl)thio)methyl)-4Hchromen-4-one Methanol Solvate [J].
孙海燕 .
结构化学, 2014, 33 (10) :1467-1471
[15]   Synthesis and Anticonvulsant Activity of Novel 3-(2-(4H-1,2,4-triazol-4-yl)ethyl)-1-alkyl-1H-indole Derivatives [J].
Liu, Chuan-Feng ;
Zhang, Hong-Jian ;
Quan, Zhe-Shan .
Letters in Drug Design & Discovery, 2016, 13 (08) :833-839
[16]   Synthesis, structure, and biological activity of novel 1H-1,2,4-Triazol-1-yl-thiazole derivatives [J].
Shao Ling ;
Zhou Xin ;
Zhang Qing ;
Liu Jian-Bing ;
Jin Zhong ;
Fang Jian-Xin .
SYNTHETIC COMMUNICATIONS, 2007, 37 (1-3) :199-207
[17]   Synthesis, molecular docking and α-glucosidase inhibition of 2-((5,6-diphenyl-1,2,4-triazin-3-yl)thio)-N-arylacetamides [J].
Wang, Guangcheng ;
Li, Xin ;
Wang, Jing ;
Xie, Zhenzhen ;
Li, Luyao ;
Chen, Ming ;
Chen, Shan ;
Peng, Yaping .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2017, 27 (05) :1115-1118
[18]   Synthesis, structure and biological activity of 2-{5[(1H-1,2,4-triazol-1-yl)methyl]-4-phenyl-4H-1,2,4-triazol-3-ylthio}-1-arylethanone [J].
Hu, Zhi-Qiang ;
Yang, Ya-Xun ;
Zhang, Gong-Sheng ;
Li, Kai ;
Xu, Liang-Zhong .
CHINESE JOURNAL OF ORGANIC CHEMISTRY, 2007, 27 (03) :419-423
[19]   Synthesis, In silico studies and antitumor activity of new 4-bro-mo-2-(1H-1,2,4-triazol-3-yl)aniline derived schiff bases [J].
Shivaraja, G. ;
Majid, Fadzilah Adibah Abdul ;
Pradeep, S. ;
Hudiyanti, Dwi ;
Nik, Wan Mohd Norsani Wan ;
Naha, Sanay ;
Praveen, B. M. .
JOURNAL OF MOLECULAR STRUCTURE, 2025, 1345
[20]   Synthesis, antibacterial and antifungal activities of 3-(1,2,4-triazol-3-yl)-4-thiazolidinones [J].
Ozkirimli, Sumru ;
Kazan, Fusun ;
Tunali, Yagmur .
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2009, 24 (02) :447-452
12345