Study on the synthesis and biological activities of α-substituted arylacetates derivatives

Anisodamine was isolated from the medicinal herb, it was used in the treatment of gastrointestinal smooth muscle spasm, infective toxic shock and organophosphorus intoxication. But there is no report about anisodamine with α-glucosidase inhibitory activity. In order to find novel α-glucosidase inhibitors, a series of α-substituted arylacetates derivatives have been synthesized based on the active unit of anisodamine. In α-glucosidase assay, compound 9 in Schiff base form and compound 22 in ester form show strong inhibition against α-glucosidase with IC50 value of 46.81 μM and 83.76 μM, respectively. Compounds 9 and 22 exhibit comparable good antidiabetic activities as commercial drug Glimepiride. In addition, Schiff bases of α-substituted arylacetates show antitumor activities against human cancer cell lines, where compound 9 with thiourea moiety performs the best antitumor activity. We anticipate that our research will provide potential candidate scaffolds for antidiabetic drug design.

Biological activities of α-substituted arylacetates derivatives were evaluated. Compound 9 was found to be the best inhibitor against α-glucosidase with an IC50 value of 46.81 μM. It also expressed the best cytotoxic activity. Compounds 9 and 22 were effective in hypoglycemic activities.Figure optionsDownload as PowerPoint slide