Design, synthesis of 4-[2-(substituted phenyl) hydrazono]-3-(1-hydroxyethyl)-1-phenyl/methyl-3,4-dihydroquinolin-2(1H)-one derivatives and evaluation of their in vitro tyrosine kinase inhibitor activity

267-272The present investigation deals with molecular docking, synthesis, characterization, and evaluation of in vitro tyrosine kinase inhibitor activity of a series of 4-[2-(substituted phenyl) hydrazono]-3-(1-hydroxyethyl)-1-phenyl/methyl-3,4-dihydroquinolin-2(1H)-one derivatives {III-a(1-12)/III-b(1-12)}. Molecular docking studies of the title compounds were carried out using Molegro Virtual Docker (MVD-2013, 6.0) software. The MolDock scores of the derivatives ranged from (−66.508) to (−101.274); whereas the MolDock score of standard 4-anilinoquinazoline ligand was found to be (−105.219). Most of the synthesized qunolin-2-one derivatives showed better affinity towards EGFRK protein as compared to standard drug imatinib (−104.253). All the synthesized compounds were satisfactorily characterized by physical and spectral analysis (UV, IR, 1H NMR and 13C NMR and mass spectral data). Twelve derivatives were tested for their in vitro tyrosine kinase inhibitor activity using MDA-MB cell line. Compound 4-[2-(4-bromophenyl)hydrazono]-3-(1-hydroxyethyl)-1- methyl- 3,4-dihydroquinolin-2(1H)-one (III-b4) was found to be the most cytotoxic compound as compared to other synthesized derivatives, with IC50 value of 0.0515 μM against MDA- MB cell line

Design, synthesis of 4-[2-(substituted phenyl) hydrazono]-3-(1-hydroxyethyl)-1-phenyl/methyl-3,4-dihydroquinolin-2(1H)-one derivatives and evaluation of their in vitro tyrosine kinase inhibitor activity

The present investigation deals with molecular docking, synthesis, characterization, and evaluation of in vitro tyrosine kinase inhibitor activity of a series of 4-[2-(substituted phenyl) hydrazono]-3-(1-hydroxyethyl)-1-phenyl/methyl- 3,4-dihydroquinolin-2(1H)-one derivatives {III-a(1-12)/III-b(1-12)}. Molecular docking studies of the title compounds were carried out using Molegro Virtual Docker (MVD-2013, 6.0) software. The MolDock scores of the derivatives ranged from (−66.508) to (−101.274); whereas the MolDock score of standard 4-anilinoquinazoline ligand was found to be (−105.219). Most of the synthesized qunolin-2-one derivatives showed better affinity towards EGFRK protein as compared to standard drug imatinib (−104.253). All the synthesized compounds were satisfactorily characterized by physical and spectral analysis (UV, IR, 1H NMR and 13C NMR and mass spectral data). Twelve derivatives were tested for their in vitro tyrosine kinase inhibitor activity using MDA-MB cell line. Compound 4-[2-(4-bromophenyl)hydrazono]-3-(1-hydroxyethyl)-1- methyl- 3,4-dihydroquinolin-2(1H)-one (III-b4) was found to be the most cytotoxic compound as compared to other synthesized derivatives, with IC50 value of 0.0515 μM against MDA- MB cell line.

SYNTHESIS, CHARACTERISATION AND EVALUATION OF SOME 1,5-BENZODIAZEPINE QUINOLIN-2-ONE DERIVATIVES AS POSSIBLE HYPNOTIC AGENTS.

A series of novel 3-(2-(phenyl/substituted phenyl)-1H-benzo[b] [1,5]-diazepin-4-yl)-4-methoxy-1-phenyl/methylquinolin-2(1H)-one [IV-a(1-6)/IV-b(1-6)] derivatives were synthesised by condensation of 3-substituted cinnamoyl-4-methoxy-1-phenyl/methylquinolin-2(1H)-one [III-a(1-6)/III-b(1-6)] with o-phenylenediamine. The results of the docking studies revealed that the synthesised compounds exhibited well conserved hydrogen bonding with one or more amino acid residues in the active pocket of alpha1beta3gamma2L GABA(A) Receptor (PDB ID: 6HUO) using Molegro Virtual Docker Software (MVD-2013, 6.0). The title compounds exhibited Mol Dock Score in the range of -124.502 to -149.448 with score more or comparable to the standard ligand score of -127.4127 and better than the standard drug -92.3878. All the synthesized compounds were satisfactorily characterized by spectral analysis and were tested for in vivo hypnotic activity based on the potentiation of barbiturate (phenobarbitone) sleeping time in miceusing diazepam as reference standard. All the compounds, except 4-methoxy-1-methyl-3-(2-(3-nitrophenyl)-1H-benzo[b][1,5]-diazepin-4-yl) quinolin-2(1H)-one (IV-b4), significantly decreased the sleep latency, prolonged the duration of sleep and also showed good muscle relaxation property. Among the synthesised compounds, 4-methoxy-3-(2-(3-methoxyphenyl)-1H-benzo[b][1,5]-diazepin-4-yl)-1-phenylquinolin-2(1H)-one (IV-a3) was found to be the most potenthypnotic agentwith sleep latency of 26.67 ± 2.629 min and sleeping time of 111.00 ± 6.028 minutesand matches with pharmacophore mapping of the designed molecule with the MolDock score

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

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(1H)-one Ia/b has been treated with P4S10:Al2O3 to yield compound 1-(4-hydroxy-1-phenyl/methyl-2-thioxo-1,2-dihydroquinolin-3-yl)ethanone (IIa/b). Compound IIa/b has been methylated to yield compound 1-(4-methoxy-1-phenyl/methyl-2-thioxo-1,2-dihydroquinolin-3-yl)ethanone (IIIa/b) which, on condensation with ketones forms dimers giving the title compounds IVa-b (1-5). All the synthesized compounds are satisfactorily characterized by spectral data. The in silico pharmacophore modeling of the title compounds has been performed using Molegro Virtual Docker (MVD-2007 software and mGlu8 is the target and in vivo 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 (IVa-1) has been found to be −141.617. The in vivo 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 (IVa-1), 2,7-bis(4-methoxy-1-phenyl-2-thioxo-1,2-dihydroquinolin-3-yl)octa-2,6-dien-4,5-dione (IVa-2), 2,6-bis(4-methoxy-1-methyl-2-thioxo-1,2-dihydroquinolin-3-yl)hepato-2,5-dien-4-one (IVb-2) and (2E,6E)-2,6-bis(4-methoxy-1-phenyl-2-thioxo-1,2-dihydroquinolin-3-yl) cyclohexanone (IVb-4) have been found to be most potent against pentylenetetrazole induced convulsion

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

544-550This 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(1H)-one Ia/b has been treated with P4S10:Al2O3 to yield compound 1-(4-hydroxy-1-phenyl/methyl-2-thioxo-1,2-dihydroquinolin-3-yl)ethanone (IIa/b). Compound IIa/b has been methylated to yield compound 1-(4-methoxy-1-phenyl/methyl-2-thioxo-1,2-dihydroquinolin-3-yl)ethanone (IIIa/b) which, on condensation with ketones forms dimers giving the title compounds IVa-b (1-5). All the synthesized compounds are satisfactorily characterized by spectral data. The in silico pharmacophore modeling of the title compounds has been performed using Molegro Virtual Docker (MVD-2007 software and mGlu8 is the target and in vivo 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 (IVa-1) has been found to be −141.617. The in vivo 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 (IVa-1), 2,7-bis(4-methoxy-1-phenyl-2-thioxo- 1,2-dihydroquinolin-3-yl)octa-2,6-dien-4,5-dione (IVa-2), 2,6-bis(4-methoxy-1-methyl-2-thioxo-1,2-dihydroquinolin-3- yl)hepato-2,5-dien-4-one (IVb-2) and (2E,6E)-2,6-bis(4-methoxy-1-phenyl-2-thioxo-1,2-dihydroquinolin-3-yl) cyclohexanone (IVb-4) have been found to be most potent against pentylenetetrazole induced convulsion

Synthesis, characterisation and evaluation of some 1,5-benzodiazepine quinolin-2-one derivatives as possible hypnotic agents

849-857A series of novel 3-(2-(phenyl/substituted phenyl)-1H-benzo[b] [1,5]-diazepin-4-yl)-4-methoxy-1-phenyl/methylquinolin-2(1H)-one [IV-a(1-6)/IV-b(1-6)] derivatives are synthesised by condensation of 3-substituted cinnamoyl-4-methoxy-1-phenyl/methylquinolin-2(1H)-one [III-a(1-6)/III-b(1-6)] with o-phenylenediamine. The results of the docking studies reveal that the synthesised compounds exhibited well conserved hydrogen bonding with one or more amino acid residues in the active pocket of alpha1beta3gamma2L GABA(A) Receptor (PDB ID: 6HUO) using Molegro Virtual Docker Software (MVD-2013, 6.0). The title compounds exhibit Mol Dock Score in the range of -124.502 to -149.448 with score more or comparable to the standard ligand score of -127.4127 and better than the standard drug -92.3878. All the synthesized compounds were satisfactorily characterized by spectral analysis and were tested for in vivo hypnotic activity based on the potentiation of barbiturate (phenobarbitone) sleeping time in miceusing diazepam as reference standard. All the compounds, except 4-methoxy-1-methyl-3-(2-(3-nitrophenyl)-1H-benzo[b][1,5]-diazepin-4-yl) quinolin-2(1H)-one (IV-b4), significantly decrease the sleep latency, prolonged the duration of sleep and also showed good muscle relaxation property. Among the synthesised compounds, 4-methoxy-3-(2-(3-methoxyphenyl)-1H-benzo[b][1,5]-diazepin-4-yl)-1-phenylquinolin-2(1H)-one (IV-a3) is found to be the most potenthypnotic agentwith sleep latency of 26.67 ± 2.629 min and sleeping time of 111.00 ± 6.028 minutesand matches with pharmacophore mapping of the designed molecule with the MolDock score