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<p>Docking, synthesis, and characterization of novel heterocyclic ring system and their evaluation for mGlu8 receptor agonist as anticonvulsant agents</p>

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Title Statement <p>Docking, synthesis, and characterization of novel heterocyclic ring system and their evaluation for mGlu8 receptor agonist as anticonvulsant agents</p>
 
Added Entry - Uncontrolled Name Naik, Sindiya D; Department of Pharmaceutical Chemistry, PES’s Rajaram and Tarabai Bandekar College of Pharmacy, Farmagudi, Goa 403 401, India
Chandavarkar, Sachin K; Department of Pharmacognosy, ASPM College of Pharmacy, Sangulwadi, Dist. Sindhudurg 416 810, India
Tawade, Shilpa S; Department of Pharmaceutical Chemistry, PES’s Rajaram and Tarabai Bandekar College of Pharmacy, Farmagudi, Goa 403 401, India
Shingade, Sunil G; Department of Pharmaceutical Chemistry, SSP’s V P College of Pharmacy, Madkhol, Dist. Sindhudurg 416 510, India
Palkar, Mahesh B; Department of Pharmaceutical Chemistry, KLEU’s College of Pharmacy, Hubli 580 031, India
Desai, Shivalingrao N Mamle; Department of Pharmaceutical Chemistry, PES’s Rajaram and Tarabai Bandekar College of Pharmacy, Farmagudi, Goa 403 401, India
 
Uncontrolled Index Term Quinolin-2(1H)-one, anticonvulsant, mGlu8 receptor, phenylenetetrazole
 
Summary, etc. <p style="text-align: justify;">This research work involves the synthesis of a series of substituted 1-(4-methoxy-1-phenyl/methyl-2-thioxo-1,2-dihydroquinolin-3-yl)ethanone [IVa/b(1-5)] derivatives by dimerization at third position and evaluation of their anticonvulsant activity. The starting material 3-acetyl-4-hydroxy-1-phenyl/methylquinolin-2(1<em>H</em>)-one <strong>Ia/b</strong> has been treated with P<sub>4</sub>S<sub>10</sub>:Al<sub>2</sub>O<sub>3</sub> to yield compound 1-(4-hydroxy-1-phenyl/methyl-2-thioxo-1,2-dihydroquinolin-3-yl)ethanone (<strong>IIa/b</strong>). Compound <strong>II</strong>a/b has been methylated to yield compound 1-(4-methoxy-1-phenyl/methyl-2-thioxo-1,2-dihydroquinolin-3-yl)ethanone (<strong>III</strong>a/b) which, on condensation with ketones forms dimers giving the title compounds <strong>I</strong><strong>Va-b </strong>(<strong>1-5</strong>). All the synthesized compounds are satisfactorily characterized by spectral data. The <em>in silico</em> pharmacophore modeling of the title compounds has been performed using Molegro Virtual Docker (MVD-2007 software and mGlu8 is the target and <em>in vivo </em>anticonvulsant activity by phenylenetetrazole (PTZ) induced convulsion method. The results of docking have revealed that the synthesized compounds exhibit well-conserved hydrogen bonds with one or more amino acid residues in the active pocket of metabotropic glutamate receptor mGluR8 complexed with (S)-3,4-dicarboxyphenylglycine (DCPG) (PDB ID:6E5V)LY341495 antagonist (PDB ID: 3MQ4). The MolDock Score of compound 2,6-bis(4-methoxy-1-phenyl-2-thioxo-1,2-dihydroquinolin-3-yl)hepato-2,5-dien-4-one (<strong>IVa-1</strong>) has been found to be −141.617. The <em>in vivo </em>anticonvulsant activity results show that compound 2,6-bis(4-methoxy-1-phenyl-2-thioxo-1,2-dihydroquinolin-3-yl)hepato-2,5-dien-4-one (<strong>IVa-1</strong>), 2,7-bis(4-methoxy-1-phenyl-2-thioxo-1,2-dihydroquinolin-3-yl)octa-2,6-dien-4,5-dione (<strong>IVa-2</strong>), 2,6-bis(4-methoxy-1-methyl-2-thioxo-1,2-dihydroquinolin-3-yl)hepato-2,5-dien-4-one <strong>(IVb-2</strong>) and (2E,6E)-2,6-bis(4-methoxy-1-phenyl-2-thioxo-1,2-dihydroquinolin-3-yl) cyclohexanone (<strong>IVb-4</strong>) have been found to be most potent against pentylenetetrazole induced convulsion.</p>
 
Publication, Distribution, Etc. Indian Journal of Chemistry (IJC)
2022-05-31 17:21:39
 
Electronic Location and Access application/pdf
http://op.niscair.res.in/index.php/IJC/article/view/63647
 
Data Source Entry Indian Journal of Chemistry (IJC); ##issue.vol## 61, ##issue.no## 5 (2022): Indian Journal of Chemistry-(IJC)
 
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