2-Aminobenzimidazole conjugates of NSAIDS: novel compounds with immunomodulatory, anti-inflammatory and antioxidant actions

Abstract

2-Aminobenzimidazole (ABZ) and guanidine have immunomodulatory activity, whereas NSAIDs have anti-inflammatory activity. We, therefore, developed several novel ABZ-NSAID conjugate compounds and tested their anti-inflammatory and immunomodulatory activities. We also measured their antioxidant and ulcerogenic properties. We found that all compounds had not only anti-inflammatory activity but they also had immunomodulatory and antioxidant activities. While compound 2 had immunostimulatory activity (humoral antibody titre, HAT 7.2 ± 0.20 and carbon clearance index, K 0.030 ± 0.001), compound 9 had immunosuppressive activity (HAT 3.4 ± 0.24 and K 0.012 ± 0.002). These two compounds did not produce ulcers and hence were safe to the gastric mucosa. In addition, we used Lipinski’s parameters and found that all compounds had drug-like properties. Thus, we have provided new evidences to use compounds 2 and 9 for the treatment of inflammatory and immunomodulatory disorders like rheumatoid arthritis, ulcerative colitis, multiple sclerosis, osteoarthritis and cancer.