Hitoshi Arai

Comparison of uptake of mitomycin C and KW-2149 by murine P388 leukemia cells sensitive or resistant to mitomycin C

SummaryKW-2149, a new mitomycin C (MMC) derivative, inhibited the growth of murine P388 leukemia in vitro at 20-fold lower concentrations than those of MMC. KW-2149 was also effective in inhibiting the growth of MMC-resistant P388 (P388/MMC) cells. To elucidate these characteristics of KW-2149, its uptake and efflux were compared with those of MMC in MMC-sensitive and-resistant P388 cells. Both MMC and KW-2149 accumulated rapidly in P388 cells after incubation at the concentration of 0.47 and 0.024 μm, respectively, which were the IC50 values at 1-h exposure. Although this concentration of KW-2149 was 20 times lower than that of MMC, its intracellular concentration was little more than that of MMC, suggesting that KW-2149 accumulated in the cells quite efficiently. The accumulated KW-2149 in the cells after 1-h treatment remained for as long as 24 h after the incubation of the cells in drug-free medium, suggesting that most of the intracellular KW-2149 or MMC was bound to cellular components. The ratios of resistance of P388/MMC cells to MMC and KW-2149 were 34 and 8.8, respectively, at 1-h exposure, suggesting that P388/MMC cells were partially resistant to KW-2149 in vitro. P388/MMC cells also showed partial resistance to cisplatin, Adriamycin,m-AMSA, and etoposide. The accumulation of MMC in P388/MMC cells was lower than that in P388 cells, although the size of the former cells was almost equal to that of the latter. As a result, the amount of DNA-bound MMC was lower in P388/MMC cells than in P388 cells, suggesting its involvement in the mechanisms of MMC resistance in P388/MMC cells.

Review: Anti-infectives Novel mitomycin derivatives

Modification studies describing the synthesis of a number of mitomycin derivatives that have appeared in the patent literature during recent years are reviewed. Particular emphasis is placed on the design of the derivatives and their preparation. Biological activities, reaction schemes and structure-activity relationships for the derivatives are also mentioned in this review.

An unusual replacement of a methylene moiety by a phenylseleno group. Synthesis of mitomycin C labelled at C-6 by 13CH3 and C2H3

A novel replacement of the C-6-methylene group of 7,7-ethylenedioxy-6-methylenemitosane by a phenylseleno group was employed to prepare a critical intermediate in the synthesis of mitomycin C labelled at C-6 by 13CH3 and C2H3.