Synthesis,characterisation, and biological activity of three new amide prodrugs of lamotrigine with reduced hepatotoxicity |
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Authors: | Saurabh K Sinha Prabhat K Shrivastava Sushant K Shrivastava |
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Institution: | (1) Department of Pharmaceutics, Institute of Technology, Banaras Hindu University, 221005 Varanasi, Uttar Pradesh, India; |
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Abstract: | Lamotrigine (LTG) is an antiepileptic drug used for the prevention of convulsions. Except several known side effects, hepatic
dysfunction is also reported. Hepatotoxic side effects occur due to the dichlorophenyl moiety which develops an abnormally
low level of glutathione. Depletion of glutathione causes oxidative stress and hepatic cell damage. The goal of the present
study was to test the action and side effects of the three compounds synthesised and compared to LTG. Three amide prodrugs
of LTG were synthesised by its reaction with N-acetylamino acids, viz, glycine, glutamic acid, and methionine. Purified synthesised prodrugs were subjected to thin layer
chromatography, melting point, solubility and partition coefficients determination and characterised by UV, FTIR, 1H and 13C NMR spectroscopy. The synthesised prodrugs were subjected to in vitro hydrolysis and to anticonvulsant and hepatotoxic activity
studies. Significant reduction in hepatotoxicity and comparable anticonvulsant activities were obtained in all synthesised
prodrugs as compared to LTG. |
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Keywords: | |
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