Regeneration characteristics of mitomycin C-dextran conjugate in relation to its activity.

Abstract

The regeneration characteristics and biological activities of mitomycin C-dextran conjugate (MMC-D) were investigated in comparison with those of free mitomycin C (MMC), and the following results were obtained. (1) MMC is coupled at the 1a-nitrogen position via an amide linkage to a carboxyl group of ε-aminocaproic acid (6-aminohexanoic acid) which was introduced onto dextran as a spacer. (2) MMC-D was stabler than MMC against acid-catalyzed and metabolic degradation. (3) MMC was liberated from MMC-D with a half-life of about 24 h under physiological conditions (pH 7.4, 37°C) and more rapidly at higher pH. (4) Liver homogenate did not accelerate the liberation of MMC from MMC-D. (5) Antimicrobial activity of MMC-D against Escherichia coli B was less than one-eighteenth of that of MMC. (6) MMC-D showed about one-tenth of the antitumor activity of MMC in vitro in contact with L1210 leukemia cells, but showed almost equal efficiency in the i. p.-i. p. system in vivo, suggesting that MMC-D exhibited activity after being regenerated to the parent drug in the body.