SYNTHESIS AND PRELIMINARY ANTICANCER STUDY OF 5-FLUOROURACIL-PHTHALIMIDE CONJUGATE UTILIZING MOLECULAR HYBRIDIZATION APPROACH

Abstract

Cancer is still the most challenging disease in the entire world. Molecular hybridization is very interesting approach in design of drug and development depends on the combination of pharmacophoric moieties of two pharmacologically active compounds results in a new hybrid compound with better affinity and efficacy, when compared to the parent drugs. The aim of the present study is to synthesize new 5-fluorouracil derivatives as probable more active anticancer agents than the parent drug. 5-fluoro-4-oxo-1,4-dihydropyrimidin-2-yl2-(1,3-dioxoisoindolin-2-ylamino) acetate [IV] and 2-(2-(5- fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-oxoethylamino) isoindoline-1,3-dione [V] have been synthesized utilizing hybridization approach from 5-fluorouracil and phthalimide through amino acetate or 2-oxoethylamino linkers. The structures of the newly synthesized compounds and their intermediates were characterized by FT-IR,13C-NMR ESI-MS spectral analysis. A preliminary cytotoxicity study that evaluated by crystal violet assay using a target breast cancer cell, murine mammary adenocarcinoma cell line indicates that the compounds have considerable anticancer activity relative to the lead one.