In Silico Analysis: Anti-Inflammatory and α-Glucosidase Inhibitory Activity of New α-Methylene-γ-Lactams.

The research about α-methylene-γ-lactams is scarce; however, their synthesis has emerged in recent years mainly because they are isosters of α-methylene-γ-lactones. This last kind of compound is structurally most common in some natural products' nuclei, like sesquiterpene lactones that show biological activity such as anti-inflammatory, anticancer, antibacterial, etc., effects. In this work, seven α-methylene-γ-lactams were evaluated by their inflammation and α-glucosidase inhibition. Thus, compounds 3-methylene-4-phenylpyrrolidin-2-one ( 1 ), 3-methylene-4-(p-tolyl)pyrrolidin-2-one ( 2 ), 4-(4-chlorophenyl)-3-methylenepyrrolidin-2-one ( 3 ), 4-(2-chlorophenyl)-3-methylenepyrrolidin-2-one ( 4 ), 5-ethyl-3-methylene-4-phenylpyrrolidin-2-one ( 5 ), 5-ethyl-3-methylene-4-(p-tolyl)pyrrolidin-2-one ( 6 ) and 4-(4-chlorophenyl)-5-ethyl-3-methylenepyrrolidin-2-one ( 7 ) were evaluated via in vitro α-glucosidase assay at 1 mM concentration. From this analysis, 7 exerts the best inhibitory effect on α-glucosidase compared with the vehicle, but it shows a low potency compared with the reference drug at the same dose. On the other side, inflammation edema was induced using TPA (12- O -tetradecanoylphorbol 13-acetate) on mouse ears; compounds 1 - 7 were tested at 10 µg/ear dose. As a result, 1 , 3 , and 5 show a better inhibition than indomethacin, at the same doses. This is a preliminary report about the biological activity of these new α-methylene-γ-lactams.