In vitro antitumour activity of cis - and trans -5-fluoro-5,6-dihydro-6-alkoxy-uracils; effects on thymidylate synthesis

摘要: A class of new 5-fluorouracil (FU) analogues, the 5-fluoro-5,6-dihydro-6- alkoxy-uracils was synthesised with a modification at 6-position pyrimidine ring. At this position analogues have hydroxy or alkoxy group different chain lengths either in cis- trans-configuration. The antiproliferative effect these compounds tested on five cell lines origin. Generally, cis-configuration had higher activity than those growth inhibitory decreased increasing length, but compound lowest effect. One analogue, cis-5-F-5,6-dihydro-6-methoxy-uracil FU one lines. Effects thymidylate synthase (TS), possible target were evaluated by thymidine rescue inhibition and incorporation tritiated deoxyuridine (3H-UdR) into DNA. In solid tumour addition TdR reversed Inhibition TS intact cells determined measuring 3H-UdR two 2- to 5-fold stronger that both All other produced equimolar equi-toxic concentration. Concluding from results we regard as most promising analogue series, because its marked cells.