Synthesis, hydrolysis studies and phamacodynamic profiles of amide prodrugs of dexibuprofen with amino acids.
The present investigation deals with the synthesis of novel prodrugs of dexibuprofen with amino acids with an aim to achieve potent anti-inflammatory activity and less gastrointestinal toxicity. Structures of synthesized compounds were confirmed by spectral and elemental analyses. In vitro hydrolytic studies in simulated intestinal fluid, 80% plasma and rat faecal matter showed satisfactory release of dexibuprofen due to enzymatic cleavage. The synthesized prodrugs were evaluated for anti-inflammatory activity, analgesia, ulcerogenicity and histopathology. The anti-inflammatory activity of dexibuprofen was 43.3% whereas an improved value of 73.4, 77.3, 72.8 and 64.5% was observed for the synthesized prodrugs. The percentage analgesia of the prodrugs increased, whereas a decrease in the mean ulcer index values than dexibuprofen was observed. The histopathological studies revealed less ulceration in the gastric region when treated with prodrugs. Thus, the prodrugs were proved to be better in action as compared with the parent drug.
Department of Pharmaceutical Chemistry, Sree Vidyanikethan College of Pharmacy, Sree Sainath Nagar, Tirupati, Andhra Pradesh, India. arunrasheed@rediffmail.com
Arun
A
Rasheed
C K Ashok
CK
Kumar
Ashutosh
A
Mishra
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D055598:Chemical Phenomena / Q000187:drug effects; D005243:Feces / Q000737:chemistry; D006801:Humans; D006868:Hydrolysis; D007052:Ibuprofen / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D015394:Molecular Structure; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced
D000577:Amides; D000596:Amino Acids; D000700:Analgesics; D000893:Anti-Inflammatory Agents; D011355:Prodrugs; C539402:dexibuprofen; D007052:Ibuprofen