Synthesis and Anticonvulsant Screening of Some Potentially Active Oximes

Ahmed Rufa’i1*, Abdullahi Y. Idris1, Aliyu Musa2, Mohammed G. Magaji3
1Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria, Nigeria.
2Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria, Nigeria.
3Department of Pharmacology and Therapeutic, Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria, Nigeria.

Corresponding Author: roofmoon4cool@gmail.com; Tel: +2347068296718
Recieved Date: February 25, 2020; Accepted Date: April 05, 2020; Published Date: 30 April 2020
Citation: Rufa’i A, Idris AY, Musa A, Magaji MG. Synthesis and Anticonvulsant Screening of Some Potentially Active Oximes. Trop J Nat Prod Res. 2020; 4(4):131-135.  https://doi.org/10.26538/tjnpr/v4i4.3
Copyright: © 2020 Rufa’i et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
ABSTRACT

Neurological disorders such as epilepsy remain a major concern to public health despite considerable efforts aimed at developing effective medicine. This work reports the synthesis and anticonvulsant screening of four oximes; (E)-N-hydroxy-1-phenylmethanimine (EHPM), (Z)-N-hydroxy-1-phenylmethanimine (ZHPM), (1E,2E)-N,NI-dihydroxy-1,2-diphenylathane-1,2-diimine (EEDDP-E) and (1E,2E)-N,NI-dihydroxy-1,2-diphenylethane-1,2-diimine (ZEDDPE). The compounds were synthesized from the reaction between various carbonyl compounds and hydroxylamine using Beckmann rearrangement reaction. The structures of the synthesized compounds were established using Ultraviolet (UV), Infrared (IR), Proton and Carbon-13 nuclear magnetic resonance (NMR) spectroscopy. The compounds were screened for anticonvulsant activity using maximal electroshock (MES) test in chicks and subcutaneous pentylenetetrazole (scPTZ) seizure test in mice. The neurotoxicity of the compounds was investigated using beam walking assay in mice. In maximal electroshock seizure (MES), model only compound EHPM protected 60% at a dose of 56 mg/kg (0.5%). The other oximes synthesized were generally inactive. However, in subcutaneous pentyleneterazole (scPTZ)-induced seizure test three compounds showed good activity viz: EHPM (83.33%) and ZHPM (66.67%). Compound ZEDDPE provided 100% protection at a dose of 300 mg/kg. The significant activity of the compounds against pentylenetetrazole (scPTZ)-induced seizure suggests that they may be beneficial in absence and complex partial seizures. The moderate activity of EHPM against maximal electroshock is suggestive of potential in generalized tonic-clonic seizure.  All the synthesized oximes were found not to produced significant motor coordination deficit at the doses tested indicating that they are not neurotoxic and are therefore recommended for further screening and optimization.

Keywords: Synthesis; imine; maximal electroshock; neurotoxicity; oximes; pentylenetetrazole.
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