Open AccessSynthesis, characterization and biological evaluation of some glutathione inducing amino acid conjugates of valproic acid with reduced hepatotoxicity
Author(s) -
Saurabh Sinha,
Praveen Bhoopathi,
Prabhat K. Shrivastava,
Sushant K. Shrivastava
Publication year - 2012
Publication title -
asian pacific journal of tropical disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.208
H-Index - 33
ISSN - 2222-1808
DOI - 10.1016/s2222-1808(12)60155-8
Subject(s) - chemistry , prodrug , conjugate , glutathione , glycine , anticonvulsant , in vivo , hydrolysis , valproic acid , amino acid , chromatography , organic chemistry , biochemistry , enzyme , mathematical analysis , mathematics , microbiology and biotechnology , neuroscience , epilepsy , biology
Objective: To synthesis and evaluate three glutathione inducing amino acid conjugates of\udvalproic acid (VPA) and compare with the same VPA to diminish its hepatotoxicity. Methods:\udPurified synthesised prodrugs were subjected to thin layer chromatography, melting point,\udsolubility studies and characterised by UV, FTIR, 1H, 13C NMR and elemental analysis. The\udsynthesised prodrugs were subjected to in vitro hydrolysis in various buffer solution (pH 1.2, 7.4,\ud9.0) and in vivo anticonvulsant, hepatotoxic activity studies. Result: Three synthesized conjugates\udwere assumed to be in agreement with the anticipated structures. All the three conjugates were\udalso able to prevent seizures in experimental rats with a comparable activity as the parent drug,\udVPA. Among the three conjugates, the glycine conjugate showed better anticonvulasant activity\udcompared to glutamic acid and cystine conjugates. Conclusions: Significant reduction in\udhepatotoxicity and comparable anticonvulsant activities were obtained in all synthesised prodrugs\udas compared to VPA