Psychomotor Seizure Screening and in vitro Neuroprotection Assay of Hydrazones Derived from 2-Acetyl Thiophene

Title:Psychomotor Seizure Screening and in vitro Neuroprotection Assay of Hydrazones Derived from 2-Acetyl Thiophene

Volume: 17 Issue: 1

Author(s): Bijo Mathew, Githa E. Mathew, Jerad Suresh, Mohammed Jaseel, D. Usman, P. N. Shiva Subramanyan, Kallivalappil F. Safna and Jobin K. Vilapurathu

Affiliation:

Keywords: Anticonvulsant activity, 2-acetyl thiophene, hydrazone, neuroprotection.

Abstract: Background: Hydrazone core is a versatile structural linker for the development of various classes of antiepileptic agents. The aim of this study was to investigate the anticonvulsant activity of thiophene based hydrazones according to the antiepileptic drug development program protocol.

Methods: The maximal electroshock-induced seizure and 6 Hz "Psychomotor" seizure test models in mice were performed. Additionally, the active compounds in the screening test were subsequently subjected to the maximal electroshock-induced seizure test that allowed determination of their median effective doses and median toxic doses. The most active compound was also subjected to the In vitro Hippocampal slice culture neuroprotection assay.

Results: Among the synthesized compounds, 1-(thiophen-2-yl) ethylidene] hydrazine carboxamides (THb) and 1-(thiophen-2-yl) ethylidene] hydrazine carbothioamide (THc) showed a broad-spectrum anticonvulsant activity since they were active in both maximal electroshock-induced seizure and 6Hz- Psychomotor induced seizure models with no neurotoxicity. In the mice maximal electroshock-induced seizure screen, compound THb gave an ED50 of 11.8 mg/kg and a TD50 of 39.47 mg/kg, resulting in a good protection index (PI), that is, TD50/ED50, of 3.3 when compared to Phenobarbital and Valproate. THb (100μM) was also found to be effectively suppressing network hyperexcitability in the in vitro mECHC spontaneous bursting model, as determined by effects on spontaneous burst activity and duration.

Conclusion: The suggested pharmacophore model for lead compounds from thiophene based hydrazones is explained by the hydrophobic domain-thiophene, electron donor-imine and hydrogen bonding domain-carboxamide or carbothioamide unit.

Cite this article as:

Mathew Bijo, Mathew E. Githa, Suresh Jerad, Jaseel Mohammed, Usman D., Subramanyan N. Shiva P., Safna F. Kallivalappil and Vilapurathu K. Jobin, Psychomotor Seizure Screening and in vitro Neuroprotection Assay of Hydrazones Derived from 2-Acetyl Thiophene, Central Nervous System Agents in Medicinal Chemistry 2017; 17 (1) . https://dx.doi.org/10.2174/1871524915999151028111728

DOI https://dx.doi.org/10.2174/1871524915999151028111728	Print ISSN 1871-5249
Publisher Name Bentham Science Publisher	Online ISSN 1875-6166