Cell Specific Cytotoxicity and Structure-Activity Relationship of Lipophilic 1-B-D-Arabinofuranosylcytosine (Ara-C) Derivatives |
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| Authors: | G. J. Peters D. A. Voorn C. M. Kuiper C. L. Van Der Wilt P. Noordhuis K. Smid |
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| Affiliation: | 1. Dept. Oncology , University Hospital VU , PO Box 7057, 1007 MB, Amsterdam;2. Norsk Hydro , Porsgrunn, Norway;3. EORTC-NDDO , Amsterdam |
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| Abstract: | Abstract Lipophilic derivatives of ara-C were developed with the aim to improve drug penetration and retention in solid tumors. Ara-C was esterified at the 5′-position with fatty acids (16–22 C-atoms, 0–3 double bonds). The derivatives were inactive in cell lines with various forms of ara-C and 2′,2′-difluorodeoxycytidine (dFdC, gemcitabine) resistance, including deoxycytidine kinase (dCK) deficiency. The activity in the parent cell lines correlated negatively with chain length and positively with double bonds. |
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