Document Detail

Design, synthesis, hydrolysis kinetics and phamacodynamic profiles of histidine and alanine conjugates of aceclofenac.
MedLine Citation:
PMID:  20228044     Owner:  NLM     Status:  MEDLINE    
The gastrointestinal toxicity associated with aceclofenac can be reduced by condensing its carboxylic acid group with methyl esters of amino acids like histidine and alanine to give amide linkage by the Schotten-Baumann method. Physicochemical characterization of the conjugates was carried out by various analytical and spectral methods. The synthesized conjugates were also subjected to in vitro hydrolysis in simulated gastric fluid (SGF) at pH 1.2, simulated intestinal fluid (SIF) at pH 7.4 and SIF+ 80% human plasma at pH 7.4. The release of free aceclofenac from histidine and alanine conjugated aceclofenac showed negligible hydrolysis in SGF compared to SIF. This indicated that the conjugates do not break in stomach, but release aceclofenac in SIF. Both synthesized conjugates showed excellent pharmacological response and encouraging hydrolysis rate in SIF and SIF + 80% human plasma. Marked reduction of the ulcer index and comparable increase in analgesic and anti-inflammatory activities were obtained in both cases compared to aceclofenac alone. These findings suggest that the conjugates are better in action compared to the parent drug and have fewer gastrointestinal side-effects.
Arun Rasheed; C K Ashok Kumar
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Acta pharmaceutica (Zagreb, Croatia)     Volume:  60     ISSN:  1846-9558     ISO Abbreviation:  Acta Pharm     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-15     Completed Date:  2010-09-23     Revised Date:  2011-08-08    
Medline Journal Info:
Nlm Unique ID:  9303678     Medline TA:  Acta Pharm     Country:  Croatia    
Other Details:
Languages:  eng     Pagination:  99-109     Citation Subset:  IM    
Department of Pharmaceutical Chemistry, Sree Vidyanikethan College of Pharmacy, Sree Sainath Nagar, Tirupati, Andhra, Pradesh-517102, India.
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MeSH Terms
Alanine / chemical synthesis*,  pharmacokinetics*,  pharmacology
Diclofenac / analogs & derivatives*,  chemical synthesis,  pharmacokinetics,  pharmacology
Drug Design*
Histidine / chemical synthesis*,  pharmacokinetics*,  pharmacology
Pain Measurement / drug effects,  methods
Rats, Wistar
Reg. No./Substance:
15307-86-5/Diclofenac; 56-41-7/Alanine; 71-00-1/Histidine; 89796-99-6/aceclofenac

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