In Silico and In Vitro Studies of the Biological Activity of 5-Substituted Derivatives of N¹-Carboxymethyl-5-Fluorouracil: Potential 5-Fluorouracil Prodrugs

The probable cytotoxic activity, probable hematotoxicity, and probable acute toxicity on oral administration to mice (LD₅₀ mouse oral ASNN) of previously synthesized 5-substituted (Br, Cl, NO₂) derivatives of N¹-carboxymethyl-5-fluorouracil were calculated. The calculation data showed that all compounds exhibited high cytotoxic activity and low probable acute toxicity on oral administration to mice. It should be noted that in vitro investigation of cytotoxic activity (PrestoBlue, Invitrogen) showed that these compounds do not exhibit cytotoxic activity against cell lines of presumptively normal and tumor origin. The low cytotoxicity of these compounds indicated by the results of in vitro experiments will allow them to be used at quite high concentrations as compared with 5-fluorouracil for future in vivo studies.