New bioisosteric derivative of diclofenac sodium resolute gastric ulcer in rats through regulation of pro-inflammatory cytokines “Tumor necrosis factor alpha and Inter-leukin-1”

Abstract

Background and objective: Gastric ulcer is an important health risk for a human. It is a painful sore in the stomach lining. It is relatively easy to cure, but can cause significant problems if left un-treated. Non-steroidal anti-inflammatory drugs (NSAIDs) are prescribed for millions of people worldwide; however, as their consequences most of individuals suffer from gastric ulcers and related complications. Diclofenac sodium is a medication from NSAIDs class of drugs, is used to relieve joint pain from arthritis but when used chronically, it may cause bleeding and ulcers in the stomach or intestine. This study aimed to test the safety and the antiulcer activity of a new bioisosteric derivative of diclofenac sodium on a rat model. Methods: 2-Cumaranone 1 had been utilized to prepare the propanamides 2a-e then after the bioisosteric diaryl ethers 3a-e synthesized; then its purity was characterized on the basis of IR, 1HNMR and Mass spectral data. Acute toxicity on albino mice was performed to ensure the safety and an experimental rat model was used to evaluate the anti-ulcer activity. Kidney and liver functions tests were measured, ulcer measurements were reported and pro-inflammatory cytokines tumor necrosis factor alpha (TNFα) and Interleukin 1 beta (IL-1β) levels were tested. Results: Unlike diclofenac sodium, the bioisosteric diaryl ethers 3a-e is less acidic and produces less damage to the stomach wall. In addition, the structure of amide derivative is also bulky thus it is more selective to cyclooxygenase ΙΙ enzyme thus the risk of gastric ulcer was less than with diclofenac sodium itself. Conclusion: Unlike diclofenac, amide derivative of diclofenac is less acidic than diclofenac thus it produces less damage to the stomach wall.

Keywords

• gastric ulcer
• bioisosteric
• diclofenac sodium
• tn-α and il-1β