Synthesis and evaluation of N-deacetyl-N-glycosylalkylthiocolchicines as antileukemic agents

A series of N-deacetyl-N-glycosylalkylthiocolchicines (glucosyl, galactosyl, mannosyl, ribosyl, and arabinosyl) was prepared by heating N-deacetylalkylthiocolchicines with the appropriate monosaccharides in methanol. Some compounds (glucosyl-, mannosyl-, and ribosylalkylthiocolchicines) were per-O-acetylated in dry pyridine with acetic anhydride. The compounds were tested against leukemia L-1210 and P-388 systems. Preliminary results showed that the antileukemic activity of the glycosyl compounds in vitro is similar to that of the N-deacetylalkylthiocolchicines used for their preparation. However, the presence of a glycosyl moiety in the molecule gives the advantage of greater solubility in water. Of the results obtained to date in lymphoid leukemia screening in vivo, five glycosyl compounds showed promising activity levels and have now reached confirmed active status.