[Synthesis and antitumor activities of conjugates of mitomycin C-polysaccharide from Tremella fuciformis].

ABSTRACT

The conjugates of mitomycin C (MMC) with glucuronoxylomannan (AC) from Tremella fuciformis were synthesized by the use of spacers (glycine, glycylglycine, glycylglycylglycine). In i.p.-i.p. system the antitumor activity of the conjugates (MMC-G-ACP, MMC-GG-ACP, MMC-GGG-ACP) against P388 leukemia in mice was slightly lower than that of MMC by the evaluation of life span, ILS (%). In s.c.-i.p. system the antitumor activity of the conjugates against sarcoma 180 solid tumor in mice was similar to that of MMC, except for MMC-G-ACP. The reduction of the number of leukocytes caused by MMC was suppressed by attaching MMC to AC. The conjugates did not lower the cytotoxicity of MMC against L1210 mouse leukemia cells in vitro. The release rate of MMC from the conjugates in vitro (half time of MMC release MMC-G-ACP, 8.8 h; MMC-GG-ACP, 3.1 h; MMC-GGG-ACP, 2.9 h) was much faster than that of MMC-dextran, and differed in the length of the spacer. The results would give useful information on macromolecular carriers in drug-delivery system.