Synthesis and biological evaluation of novel antifolate analogs as potential anticancer treatment.

A novel process for the preparation of two ketomethylenic antifolates, 2-(2-{4-[(2,4-diamino-pteridin-6-ylmethyl)-amino]- phenyl}-2-oxo-ethyl) pentanedioic acid and 2-(2-{4-[(2,4-diamino-pteridin-6-ylmethyl)-methyl-amino]-phenyl}-2-oxo-ethyl) pentanedioic acid is described herein. Both compounds were compared with methotrexate as inhibitors of human dihydrofolate reductase and thymidylate synthase. The in-vitro and in-vivo results suggest that these novel antifolate inhibitors could potentially constitute effective therapeutic molecules in the treatment of certain cancers and might present a lower toxicity profile than methotrexate.

Determination of the 5-fluorouracil and N1(2'-furanidyl)uracil in the presence of tegafur by zero-crossing first derivative spectrometry.

A first derivative spectrometric method has been developed for the determination of the 5-fluorouracil and N1(2'-furanidyl)uracil related substances and degradation products of tegafur. The wavelengths selected for the determination of 5-fluorouracil and N1(2'-furanidyl)uracil were 298 and 288 nm, respectively. At this wavelength, the calibration graphs between the amplitude of the signals and the concentration of each compound were linear up to 24.