Rational Design and Synthesis of Diclofenac Analogues by Isosteric Replacement and Evaluation for Anti-inflammatory Activity

Abstract

Frequently called rational drug design or, simply, rational design, drug design is the innovative process of discovering new drugs characterized by the understanding of a biological target. In this research study, we made some of the first series of Schiff base (4a 4m) and imidazo (2,1 b) 1,3,4 thiadiazole (6a d) derivatives of Diclefenac as shown in Scheme. Each of the new compounds produced by the synthesis was purified through recrystallisation or column chromatography on silica (230 400mesh). Spectral data, IR, 1H NMR, were used to determine the structures of final compounds. Acute toxicity tests of synthesized compounds did not show any toxicity irrespective of a maximum dose of 2000 mg/kg of the body weight.  All the newly synthesized compounds (4a 4m and 6a 6d) were investigated to determine their anti-inflammatory activity using carrageenan induced rat paw edema method.  The synthesized compounds were effective as the anti-inflammatory compound with 73.3 percent and 70.4 percent and 71.8 percent and 70.1 percent observed in records of compound 4d and 6b, and had the most activity when compared to the reference diclofenac. As against good to moderate inhibitory activity exhibited by compounds 4a, 4c, 4g and 4i. Finally, two products out of the series of synthesized derivatives compounds (4d and 6b) have shown the most promising outcomes and might also be mentioned as possible further exploitation candidates of creating the newer anti-inflammatory agents with improved efficiency and fewer safety issues, which requires further research.