Synthesis and Pharmacological Evaluation of Tyrosine and Glycine Prodrugs of Aceclofenac

Arun Rasheed, Ashok Kumar, S. Neelufar Shama, Ashutosh Mishra


The gastrointestinal toxicity associated with aceclofenac (AC) can be reduced by synthesis of its prodrugs. It involves condensing the carboxylic acid group of AC with methyl esters of amino acids like tyrosine and glycine to give tyrosine conjugated aceclofenac (3a) and glycine conjugated aceclofenac (3b), respectively. Physicochemical characterization of the prodrugs by various analytical and spectral methods was carried out. In vitro hydrolysis in simulated gastric fluid (SGF), simulated intestinal fluid (SIF) and human plasma showed an encouraging hydrolysis rate in SIF and human plasma than in SGF. This indicated that the prodrugs do not break in stomach but release aceclofenac in SIF and human plasma. The pharmacological evaluations showed a comparable increase in anti-inflammatory activity and marked reduction of ulcer index for the prodrugs. Normal histological findings revealed that the prodrugs are not producing any ulceration in the gastric region. The prodrugs thus possess better pharmacological response than the parent drug.


NSAID, Aceclofenac, Amino Acid Prodrug, Mutual Prodrugs, Pharmacokinetics, Ulcerogenicity

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