Teratogenicity and embryotoxicity of some maleinimides

Maleinimide, the teratogenic structural "central part" of the thalidomide molecule, and 5 of its dichloro- and dibromo-derivatives have been investigated teratologically by tests on SWS mice. According to both the electrophilic properties and the spatial requirements of the substituents, the effects were found to be up to 100 times stronger than those of thalidomide, and up to 10 times stronger than those of phthalimide respectively. The results are referred to the distinct electron-acceptor behavior of the maleinimide compounds, which--due to their flat molecular structures--are able to intercalate into the DNA double helix forming EDA complexes with nucleic acid bases as electron-donor molecules. The results can be interpreted as another confirmation of Jönsson's intercalation hypothesis of the thalidomide action.