TY - JOUR

T1 - Biodegradability of Antineoplastic Compounds in Screening Tests

T2 - Influence of Glucosidation and of Stereochemistry

AU - Kümmerer, Klaus

AU - Al-Ahmad, Ali

AU - Bertram, Barbara

AU - Wiessler, Manfred

PY - 2000/4/1

Y1 - 2000/4/1

N2 - 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 β-D- glucosylisophosphoramidmustard (β-D-Glc-IPM; INN = glufosfamide) and β-L- glucosylisophosphoramidmustard (β-L-Glc-IPM). β-L-Glc-IPM has no antineoplastic effects whereas β-D-Glc-IPM is active against tumours. In contrast to IF and CP and almost all other investigated antineoplastics β-D- Glc-IPM is inherently biodegradable. Improved biodegradability of β-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. (C) 2000 Elsevier Science Ltd.

AB - 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 β-D- glucosylisophosphoramidmustard (β-D-Glc-IPM; INN = glufosfamide) and β-L- glucosylisophosphoramidmustard (β-L-Glc-IPM). β-L-Glc-IPM has no antineoplastic effects whereas β-D-Glc-IPM is active against tumours. In contrast to IF and CP and almost all other investigated antineoplastics β-D- Glc-IPM is inherently biodegradable. Improved biodegradability of β-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. (C) 2000 Elsevier Science Ltd.

KW - Antineoplastic

KW - Biodegradability

KW - Closed bottle test

KW - Glucosidation

KW - Glufosfamide

KW - Stereochemistry

KW - Zahn-Wellens test

KW - Chemistry

UR - http://www.scopus.com/inward/record.url?scp=0343485112&partnerID=8YFLogxK

U2 - 10.1016/S0045-6535(99)00451-8

DO - 10.1016/S0045-6535(99)00451-8

M3 - Journal articles

VL - 40

SP - 767

EP - 773

JO - Chemosphere

JF - Chemosphere

SN - 0045-6535

IS - 7

ER -