5-Fluorouracil 유도체 합성 및 항암작용

Synthesis and Antitumor Activity of N1-derivatives of 5-Fluorouracil

In order to find out a proper connecting bridge between 5-fluorouracil(5-FU) and a macromolecule such as a polypeptide, potentially hydrolytic N1-derivatives of 5-FU have been synthesized and evaluated for their biological activity. When tested with in vitro leukemic L1210 cells all the obtained derivatives exhibited slightly higher antitumor activity than the parent 5-FU. Among them the N1-carbamoyl analogue 2 and N1-acetamido analogue 6b showed 50% inhibition of the L1210 Cell growth at the concentrations of 5.01 X 10-8M and 1.03 X 10-7M, respectively. When tested against sarcoma 180 tumor cells inoculated into mice, the compounds 2 and 6b exhibited, respectively, 62% and 54% inhibition of the solid tumor growth at the 5-time doses of 100 mg/kg/day. Both compounds, N1-carbamoyl analogue 2 and N1-acetamido analogue 6b, released the parent 5-FU when incubated in the L1210 cell cultural media for 5 hrs.