Anticonvulsant evaluation of 2-pyrazolines carrying naphthyl moiety: An insight into synthesis and molecular docking study

Abstract

A series of N-substituted-3-(napthalen-2-yl)-5-substituted phenyl-4,5-dihydropyrazole-1-carbothioamide derivatives (4a-n) were synthesized with the view of structural requirements of pharmacophore for potential anticonvulsant agents. The synthesized compounds were assayed intraperitoneally (i.p.) and subcutaneously (s.c.) in mice against seizures induced by MES and scPTZ methods, respectively. Neurologic deficit was evaluated by rotarod method. Among the tested compounds, 4g, 4i, 4j and 4n emerged as the most active molecule in the MES model at a dose of 30 mg/kg at 0.5h comparable to standardscarbamazepine and phenytoin. In the scPTZ test,4e and 4l were found to be most active compounds at the lowest dose of 30 mg/kg at 0.5h, in the management of the convulsive disorder. Molecular docking studies of the titled compounds were also donewith 3D crystal structure of human cytosolic branched chain amino transferase (hBCATc) enzyme and compound 4e was found to have five hydrogen bond interactions with the most important active site residues.In neurotoxicity studies, except compounds 4b, 4c, 4h and 4k, rest of the compounds showed no sign of toxicity.

Synthesis of Pyrazoline Derivatives and Their Pharmacological Activities: A Review of the Last Decade

“…Miscellaneous N-substituted-3-(naphthalene-2-yl)-5-substituted phenyl-4,5-dihydro pyrazole-1-carbothioamide derivatives (154) possessed good anticonvulsant activity against the MES model at 30 mg/kg at the period of 0.5 h indicating their good ability to prevent seizure spread. [71] Fluoropyrazole-sulfonylurea and thiourea derivatives (155,156) have antidiabetic potential. However, a marked resumption in the hypoglycemic activity was seen in compounds after the cyclization of the thiourea group.…”

“…N ‐substituted‐3‐(naphthalene‐2‐yl)‐5‐substituted phenyl‐4,5‐dihydro pyrazole‐ 1‐carbothioamide derivatives ( 154 ) possessed good anticonvulsant activity against the MES model at 30 mg/kg at the period of 0.5 h indicating their good ability to prevent seizure spread [71] . Fluoropyrazole‐ sulfonylurea and thiourea derivatives ( 155 , 156 ) have antidiabetic potential.…”

Structure based drug discovery, docking modelling, synthesis and anticonvulsant pharmacological activity of new quinoline derivatives

“…Epilepsy is as a collective termfor brain function disorders that are characterized by periodic and unpredictable occurrence of seizures. The molecular docking study compound was carried out in order to assess their interaction and binding modes with target receptor and good biological activity using auto dock software [1] . We have docked the compounds in Autodock Vina docking software.…”

Synthesis, Characterization and Biological Evaluation of New 3,5-Disubstituted-Pyrazoline Derivatives as Potential Anti-Mycobacterium tuberculosis H37Ra Compounds

“…Previous studies have reported considerable biological activities when substitution occurs at position 1-, 3- and 5- of the pyrazoline ( Figure 1 ), such as anticonvulsant, antimalarial [ 2 ], anti-cardiovascular [ 3 ], anticancer [ 4 ], anti-amoebic [ 5 ], antimicrobial [ 6 , 7 ] and anti-tumor activities [ 8 ]. Meanwhile, carbothioamide derivatives were found to have significant pharmacological activities, such as monoamine oxidase (MAO) inhibitors [ 9 , 10 ], antituberculosis [ 11 , 12 , 13 ] and anticonvulsant activities [ 14 , 15 , 16 ].…”