New benzothiophene derivatives as dual COX-1/2 and 5-LOX inhibitors: synthesis, biological evaluation and docking study



El-Miligy MM, Hazzaa AA, El-Messmary H, Nassra RA, El-Hawash SA.


Future Med Chem. 2017 Apr;9(5):443-468. doi: 10.4155/fmc-2016-0230. Epub 2017 Mar 31.


AIM: Simultaneous inhibition of 5-LOX/COX may enhance anti-inflammatory effects and reduce side effects. Hence, synthesis of novel dual inhibitors of 5-LOX/COX is an important strategy for treatment of inflammation. Results/methodology: The target compounds were designed to hybridize benzothiophene scaffold or its bioisostere benzofuran with various anti-inflammatory pharmacophore hetercycles through different atoms spacers. Compounds 4a, 4c, 4d, 5b, 7a, showed significant in vitro LOX inhibitory activity higher than that of meclofenamate sodium. Compounds 4b, 4e, 4f, 5a exhibited significant in vitro COX-2 inhibition higher than celecoxib and in vitro LOX inhibitory activity twice that of reference. These compounds elicited significant in vivo anti-inflammatory activities higher than celecoxib in formalin-induced paw edema test. Compound 4e exhibited gastrointestinal safety profile as celecoxib. The results were also consistent with the docking studies. CONCLUSION: Compound 4e could be considered as structural lead for the development of a new class of anti-inflammatory agents with better safety profile.

Keywords: .

Link/DOI: 10.4155/fmc-2016-0230