Cytostatic activity of a 5-fluoro-2'-deoxyuridine-alendronate conjugate against gastric adenocarcinoma and non-malignant intestinal and fibroblast cell lines.

Background: 5-Fluoro-2'-deoxyuridine (5-FdU), a drug against gastric cancer, was covalently linked via its nucleobase with the amino-bisphosphonate alendronate (Ale), resulting in a new antimetabolite-bisphosphonate conjugate (5-FdU-Ale), designed for bone-targeting.

Materials And Methods: The cytostatic effect of 5-FdU-Ale was evaluated in vitro compared to monomers and mixtures using CASY Technologies and the human gastric adenocarcinoma cell lines 23132/87 and MKN-45, in comparison to the intestinal CCL-241 and dermal fibroblast NHDF neonatal cell lines.

Results: The adenocarcinoma cell lines demonstrated a slightly higher sensitivity, with respect to the cell lines CCL-241 and NHDF, to incubation with 5-FdU-Ale. In comparison to 5-FdU, 5-FU and an equimolar mixture of Ale+5-FdU and Ale+5-FU, the cytostatic activity of the 5-FdU-Ale was markedly reduced.

Conclusion: 5-FdU-Ale was only partially or not at all metabolized to a mixture of cytostatic metabolites in vitro. Therefore an in vivo evaluation of the conjugates is indicated.