Metal Chelates and Diabetogenic Activity II : Isoalloxazines

In a further attempt to relate the chemical structure of various compounds to their diabetogenic activity, copper chelates of several isoalloxazines, and nitrogen-containing fragments (substituted anilines) of the isoalloxazine molecules, have been prepared. All of these compounds were found to be weak chelating agents. Only copper was found to be capable of forming stable 1 : 1 chelates. The chelates of dichloro-isoalloxazines as well as the chelates of the corresponding substituted aniline compounds were found to produce a hyperglycemic response in rabbits greater than that of alloxan or its metal chelates. The chelates of dimethyl-iso- alloxazines and the corresponding substituted anilines as well as the unmetallized compounds were essentially inactive. These findings suggest that either chloro- substitution, or the presence of a sugar side chain is necessary for isoalloxazines to produce a hyperglycemic response as metal chelates.