Synthesis, characterisation, and biological activity of three new amide prodrugs of lamotrigine with reduced hepatotoxicity
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Saurabh Sinha
,
Prabhat Shrivastava
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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Artikel in diesem Heft
- Application of polyaniline as an efficient and novel adsorbent for azo dyes removal from textile wastewaters
- Enzymatic synthesis and analytical monitoring of terpene ester by 1H NMR spectroscopy
- Effect of fiber modification with carboxymethyl cellulose on the efficiency of a microparticle flocculation system
- Synthesis, crystal structure, and thermal analysis of a copper(II) complex with imidazo[4,5-f]1,10-phenantroline
- Hydrothermal synthesis of core-shell structured PS@GdPO4:Tb3+/Ce3+ spherical particles and their luminescence properties
- Optical characterisation of organosilane-modified nanocrystalline diamond films
- Synthesis, optical, and spectroscopic characterisation of substituted 3-phenyl-2-arylacrylonitriles
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- Density of the systems (NaF/AlF3)—AlPO4 and (NaF/AlF3)—NaVO3
- Semiquinol and phenol compounds from seven Senecio species
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