Biodegradability of antineoplastic compounds in screening tests: influence of glucosidation and of stereochemistry

Some pharmaceuticals such as antineoplastics are carcinogenic, mutagenic, teratogenic and fetotoxic. Antineoplastics and their metabolites are excreted by patients into waste water. In laboratory testing the frequently used isomeric anti-tumour agents cyclophosphamide (CP) and ifosfamide (IF) were shown to be not biodegradable. They are not eliminated in municipal sewage treatment plants and therefore detected in their effluents. Structural related compounds are beta-D-glucosylisophosphoramidmustard (beta-D-Glc-IPM; INN = glufosfamide) and beta-L-glucosylisophosphoramidmustard (beta-L-Glc-IPM). beta-L-Glc-IPM has no antineoplastic effects whereas beta-D-Glc-IPM is active against tumours. In contrast to IF and CP and almost all other investigated antineoplastics beta-D-Glc-IPM is inherently biodegradable. Improved biodegradability of beta-D-Glc-IPM compared to IF shows that reducing the impact of pharmaceuticals on the aquatic environment is feasible by changing the chemical structure of a given compound exerting a similar mode of action and therapeutic activity. Stereochemistry may be crucial for pharmaceutical activity of the compounds as well as for its biodegradability in the environment.