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Published on:September 2022
Indian Journal of Pharmaceutical Education and Research, 2022; 56(3s):s522-s534
Original Article | doi:10.5530/ijper.56.3s.162

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


Authors and affiliation (s):

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

1Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, SAUDI ARABIA.

2Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia, EGYPT.

3Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat, INDIA.

4Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat, INDIA

5Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, Al-Ahsa, SAUDI ARABIA.

6Department of Pharmacology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafr El-Sheikh, EGYPT.

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 be a great achievement 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 synovial 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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The Official Journal of Association of Pharmaceutical Teachers of India (APTI)
(Registered under Registration of Societies Act XXI of 1860 No. 122 of 1966-1967, Lucknow)

Indian Journal of Pharmaceutical Education and Research (IJPER) [ISSN-0019-5464] is the official journal of Association of Pharmaceutical Teachers of India (APTI) and is being published since 1967.

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