Synthesis and PASS-assisted evaluation of coumarin–benzimidazole derivatives as potential anti-inflammatory and anthelmintic agents

Abstract

Two series of novel derivatives have been designed by coupling medicinally important coumarin and benzimidazole nuclei through different linkers. These compounds have been predicted to be potent anti-inflammatory and anthelmintic by in silico studies using PASS (prediction of activity spectra for substances) software. The compounds are synthesized and evaluated for the predicted activities as well as for their in vitro antioxidant potential. Compounds of first series (4a–4f) are found good to moderate anti-inflammatory agents. Among these, compounds 4b and 4f exhibited maximum anti-inflammatory activity (45% inhibition), which is equivalent to the activity of indomethacin (48% inhibition) after 3 h (peak inflammatory response time). Compounds of second series (5a–5f) exhibit anthelmintic activity. Amongst these, compound 5f has mortality activity marginally higher than albendazole (10–11 s). Compound 5e is found to be the most potent antioxidant with remarkable EC50 value (0.08 µM/mL), which is though a little less than that of ascorbic acid (0.03 µM/mL). In addition, a comparative analysis of calculated Lipinski’s parameters reveals that all test compounds have the propensity to be orally bioavailable. Based on these findings, compounds 4b, 4f, 5e, and 5f are identified as new leads to develop potent anti-inflammatory, anthelmintic, and antioxidant compounds.