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IJPER · Lens · Functional Role of Novel Anthranilic Acid Derivatives as Anti-inflammatory Agents

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Article · Volume 56, Issue 3S · pp. S522–S534

Functional Role of Novel Anthranilic Acid Derivatives as Anti-inflammatory Agents

Mohamed A Morsy1,2, Snehal S Patel3, Pranali Parmar3, Jignasa K Savjani4, Mahmoud Kandeel5,6, Anroop B Nair1, Sabah H Akrawi1, Mahmoud El-Daly7

  1. 1Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, SAUDI ARABIA.
  2. 2Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia, EGYPT.
  3. 3Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat, INDIA.
  4. 4Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat, INDIA.
  5. 5Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, Al-Ahsa, SAUDI ARABIA.
  6. 6Department of Pharmacology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafr El-Sheikh, EGYPT.
  7. 7Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, El-Minia, EGYPT.

Abstract

Background: The discovery of new cyclooxygenase (COX) inhibitors with high efficacy and safety would greatly aid in developing anti-inflammatory drugs. This study evaluated the anti-inflammatory activity and the expected side effect of two synthesized anthranilic acid derivatives (JS-3 and JS-4).Materials and Methods: The COX selectivity of compounds was assessed in a whole blood assay. The results were confirmed by molecular docking studies.In vivo anti-inflammatory activity was tested in complete Freund’s adjuvant (CFA)-induced rheumatoid arthritis (RA) in rats. The safety profile was determined by administering a dose three times the therapeutic dose.Results: In vitro COX-2 selectivity of JS-4 was higher than JS-3 (13.70 vs. 5.56). Docking studies supported the higher selectivity of both derivatives against COX-2 than mefenamic acid. Treatment of CFA-arthritic rats with both compounds showed significant (P< 0.01) decreases in paw volume, paw thickness, arthritic index, and inflammatory parameters such as rheumatoid factor, interleukin (IL)-1β, IL-6, prostaglandin (PG) E2, PGI2, and TXB2 compared to untreated RA animals. JS-3 and JS-4 improved knee joint histopathology and protected against RA-induced pathological changes: splenomegaly, thymomegaly, and cardiomyopathy. Both derivatives produced minimal effects on liver and renal functions, without any ulcerogenic effects.Conclusion: These results suggest that JS-4 is a potential and safe candidate for managing RA without renal, liver, gastrointestinal, or cardiovascular toxicity.

Keywords: Cyclooxygenase inhibitors; Anthranilic acid derivatives; Mefenamic acid; Rheumatoid arthritis; Anti-inflammatory; Safety evaluation; Molecular docking

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