Studies on the side-chain hydroxylation of ifosfamide and its bromo analogue |
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Authors: | Misiura Konrad Kinas Ryszard W Kuśnierczyk Halina |
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Affiliation: | 1. Departamento de Química Inorgánica y Química Técnica, Facultad de Ciencias, UNED, Paseo Senda del Rey 9, E-28040 Madrid, Spain;2. Departamento de Química Inorgánica, Facultad de Ciencias Químicas, Universidad de Salamanca, Plaza de la Merced s/n, E-37008 Salamanca, Spain |
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Abstract: | Deutero-substituted (alpha,alpha,alpha',alpha'-tetradeuterated) derivatives of ifosfamide (IF-d(4)) and its bromo analogue were synthesised. In vitro metabolic studies showed that microsomal hydroxylation of IF-d(4) is slower than for unlabelled compound, suggesting that kinetic isotope effect operates during those transformations. At the same time deutero-substituted derivatives are more active against L1210 leukaemia in mice than unlabelled compounds, suggesting a negative role of side-chain hydroxylation metabolic pathways in the anticancer activity of ifosfamide and its analogues. |
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