Synthesis, anticonvulsant and toxicity evaluation of 2-(1H-indol-3-yl)acetyl-N-(substituted phenyl)hydrazine carbothioamides and their related heterocyclic derivatives (original) (raw)
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Anticonvulsant evaluation of some newer benzimidazole derivatives: design and synthesis
Acta poloniae pharmaceutica
A series of new 2-[(1-substituted phenylethylidine) hydrazine]-N-phenyl-1H-benzo[d]imidazole-1-carbothioamides (4a-n) were designed and synthesized to have the pharmacophoric elements essential for anticonvulsant activity. The key step in the synthesis of the title compounds involves the reaction of 2-mercaptobenzimidazole with hydrazine hydrate, substituted acetophenones and phenylisothiocyanate to get the compounds in good yields. All the newly synthesized compounds were screened by two most adopted models, maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ). Interestingly, compounds 4e, 4f, 4g, 4h and 4j exhibited potent anticonvulsant results and in the neurotoxicity screening, most of the compounds were devoid of toxicity at the dose of 60 and 100 mg/kg.
Medicinal Chemistry Research, 2016
A series of new benzimidazole derivatives (4ap) were synthesized and evaluated for anticonvulsant activity in albino mice against two most adopted models, i.e. maximal electroshock seizure (MES)-and subcutaneous pentylenetetrazole (scPTZ)-induced seizures. Synthesized compounds were also screened for possible neurotoxicity using rotarod test. Among the synthesized compounds, 4p showed the most promising activity in MES and scPTZ screens, which was further subjected for oral activity in rats. At a dose of 30 mg/kg, it showed tremendous activity in the scPTZ screen. The acute toxicity study (LD 50) of compounds showed that only two tested compounds 4f and 4m did not produce any mortality at any of the dose level. Molecular properties and pharmacokinetic parameters of the titled compounds were also determined using Lipinski's rule of five. The promising results encourage future investigation on the rational modification of this nucleus for development of better compounds. Keywords Anticonvulsant Á Glutamate Á Benzimidazole Á In silico Á In vivo Á Molecular docking Electronic supplementary material The online version of this article (
European Journal of Medicinal Chemistry, 2013
INTRODUCTION Epilepsy is the fourth most common neurological problem affecting human population after migrane, stroke and Alzheimer's disease (Epilepsy foundation). Epilepsy belongs to a group of neurological disorders showing neuronal hyperexcitability characterized by recurrent seizures in different parts of the brain [1]. According to WHO, it is estimated that the condition affects approximately 50 million people worldwide, 80 % of which resides in developing countries. Enormous AEDs belonging to different classes are used nowadays to treat epilepsy including phenytoin, carbamazepine, valproic acid, topiramate, gabapentin, felbamate, levetiracetam, etc. [2]. However, the current therapy using the presently available antiepileptic drugs shows limitations viz. insufficient, seizure control, unpredictability of effect and its loss, poor efficacy, inadequate information about the receptors involved, etc. Moreover AEDs do not prevent epilepsy in persons at risk of drug-resistance. Further, long term therapy with these drugs pose an array of side effects which includes but is not limited to drowsiness, ataxia, gastrointestinal disturbances, megaloblasticanaemia and hirsutism [3,4]. Hence there exists the continuous need for the discovery and development of new antiepileptic agents with higher activity, minimal or negligible toxicity and side effects. A number of heterocyclic derivatives possessing nitrogen has been reported to play an important role in pharmaceutical Design, Synthesis and Anticonvulsant Evaluation of N-[(Substituted 1H-pyrazol-3-yl)amino]-2-(4-methylphenyl)quinazolin-4(3H)-one Derivatives
Medicinal Chemistry Research, 2017
1,5-Diaryl-1H-1,2,4-triazole-3-carboxamide derivatives were designed, synthesized, and evaluated for its anticonvulsant activity using maximal electroshock (MES) and chemoshock (scPTZ and Strychnine) animal screen methods. Neurotoxicity was also assessed. In MES model, compound 4f showed 100% of phenytoin activity after both 0.5 and 4 h. In scPTZ model, compound 4e showed 100% of sodium valproate activity. In Strychnine model, compound 4e showed 120% more delay of onset of convulsion and 124% more delay of time of death relative to sodium valproate. Most of the target compounds showed mild neurotoxicity especially compound 4f which showed excellent activity against electroshock. Pharmacophoric study reveals that the synthesized compounds showed good fitting on the pharmacophoric query with good RMSDX results.
IP Innovative Publication Pvt. Ltd., 2018
Several new promising bioactive derivatives of N-(5-(Substituted)-1, 3, 4-thiadiazol-2-yl)-2-((5-(substitutes)-4H-1, 2, 4-triazol-3-yl) amino) acetamide were synthesized. The compounds were obtained in excellent yields. The synthesized compounds were confirmed on the basis of IR and NMR. Acute toxicity study was done to determine the LD50 of the newly synthesized compounds. Some of the synthesized compounds were evaluated for their anticonvulsant effect by PTZ induced convulsions method. Statistical testing was done by one way ANOVA followed by Dunnett’s test. The compounds D-III showed the highest percentage of protection as compared to PTZ, i.e. 80% at the dose of 20mg/kg among the evaluated compounds compared to control. Keywords: 1, 3, 4-thiadiazole, 1, 2, 4-triazole, Anticonvulsant.
TheScientificWorldJournal, 2014
Anticonvulsant potential and neurotoxicity of certain new imidazole-containing arylsemicarbazones 6a-p are reported. The test compounds 6a-p exhibited anticonvulsant activity mainly in the scPTZ screen. Compound 6p emerged as the most active surrogate displaying 100% protection at a dose level of 636 μ mol/kg in the scPTZ screen without any neurotoxicity. The assigned (E)-configuration of the title compounds 6a-p was confirmed via single crystal X-ray structure of compound 6g.
Advances in Pharmacology and Pharmacy, 2023
Introduction: Benzimidazole is a heterocyclic hydrocarbon having unique basic structural characteristics in their structure. This moiety was formed by using aromatic benzene and imidazole heterocylic ring. This molecule gives great application in biological and clinical studies. Benzimidazole and its derivatives have versatile Nitrogen containing heterocyclic compounds that give a promising category of biologically active compounds and possess a wide selection of biological activities like antibacterial drug, medicament, anti-ulcer, anti-diabetic, etc. Objective: Several scientists have declared that benzimidazole system possesses the variable sites like the position of a pair and five which might be fittingly changed to yield potent therapeutic agents. The current review covers the chemistry and medicine activities of substituted benzimidazoles. Materials & Methods: Formic acid; Acetyl Chloride; Hydrazine; Benzene-1,2-diol; Glycolic Acid; Benzoyl Chloride; Methyl Chloride; Ethyl Chloride; Benzamide etc. and methods are TLC, IR spectra, 1 H-NMR and MS. Results & Conclusion: The pharmacological screening was done by using PTZ Induced Convulsion Method for anticonvulsant activity. The synthesize compounds were established to be BA to BK. The compound BA, BC, BJ, BI and BK were established to be the most potent compound through the comparison with standard drugs phenytoin. Synthesized newer benzimidazole derivatives were screened for Anti-convulsant activity. It was seen that in biological activity, derivatives containing 2-nitro aniline and 3-nitro aniline have more significant biological activities than other benzimidazole derivatives. Total 11 compounds (4 Step Products + 7 Benzimidazole Derivatives) were evaluated for their biological screening.
A series of N,N-dialkylaminoalkoxy-2-Oxo-indole-3-ylideneBenzohydrazides were synthesized by using the well designed synthetic route and the purity of the compounds were assessed by TLC, and characterized by FT-IR, NMR spectral data. The anti-convulsant activities of the synthesized compounds were evaluated against MES and PTZ induced seizure models in mice. All the test compounds were administered at doses of 50mg/kg body weight orally for MES method. The stimulus parameters in mice were 50mA in a pulse of 60Hz for 200ms. Intraperitonially for a PTZ method from the series of compounds it was noted that compound N,N-dimethylaminoPropoxy-2-Oxo-5-methyl-3-ylidenebenzo hydrazides(VIIb) protected more than 80% of the mice against MES and PTZ induced seizures compound VIId, VIIa, VIIe were found to be next in the order of reducing the duration of convulsions in both MES and PTZ methods. Molecular docking studies were also carried out by using windows 2007 using Moe 2008.10 version. The 5HT 2c mouse receptor was retrieved from the protein data bank and used as target receptor was retrieved from the protein data bank.
Synthesis and Anticonvulsant Activities of Some Triazolothiadiazole Derivatives
Archiv der Pharmazie, 2012
The present study describes the synthesis and anticonvulsant activity evaluation of 6-substituted-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives (4a-4x) and their partially dehydrogenated products 5,6-dihydro-6-substituted-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives (5a-5n). The bioevaluation demonstrated that most compounds in the series of 4a-4x exhibited potent anticonvulsant activity in the maximal electroshock test. Among which, 6-(4-chlorophenyl)-[1,2,4]triazolo[3,4b][1,3,4]thiadiazole (4h) emerged as the most promising candidate on the basis of its favorable ED 50 value of 23.7 mg/kg and PI value of 10.8. In addition, the potency of compound 4h against seizures induced by pentylenetetrazole, 3-mercaptopropionic acid, and bicuculline in the chemicalinduced seizure tests suggested that compound 4h displayed broad-spectrum activity in several models, and it may exert its anticonvulsant activity through affecting the GABAergic system.
TheScientificWorldJournal, 2014
Keeping in view the structural requirements suggested in the pharmacophore model for anticonvulsant activity, a new series of 3-(2-(substitutedbenzylidene)hydrazinyl)-N-(substituted benzo[d]thiazol-2-yl)-propanamides were synthesized with aromatic hydrophobic aryl ring (A), NH-C=O as hydrogen bonding domain (HBD), nitrogen atom as electron donor (D), and phenyl as distal aryl ring (C). Synthesized compounds were characterized by FTIR, (1)H NMR, (13)C NMR, mass spectroscopy, and elemental analysis. Preliminary in vivo anticonvulsant screening (phase I) was performed by two most adopted seizure models, maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ). Based on anticonvulsant screening results, two compounds, 5h and 5p, were found to be most active; they exhibited activity comparable to standard drugs phenytoin (PHY) and carbamazepine (CBZ). These active compounds were subjected to phase II and phase III screening, where they displayed much higher protecti...