Details

Autor(en) / Beteiligte

• Hitoshi, Sasaki
• Eiji, Mukai
• Mitsuru, Hashida
• Toshikiro, Kimura
• Hitoshi, Sezaki

Titel

Development of lipophilic prodrugs of mitomycin C. I. Synthesis and antitumor activity of 1a-N-substituted derivatives with aromatic pro-moiety

Ist Teil von

• International journal of pharmaceutics, 1983, Vol.15 (1), p.49-59

Ort / Verlag

Elsevier B.V

Erscheinungsjahr

1983

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• Five lipophilic la-N-substituted derivatives of mitomycin C possessing aromatic pro-moieties including benzyl, benzoyl, benzylcarbonyl, benzyloxycarbonyl, and benzoyloxymethyl groups were synthesized, and their physicochemical and biological characteristics were examined. All compounds showed increased octanol/water partition coefficients. lipophilic indexes (k') in HPLC system, and lipid solubilities. Their antimicrobial activities against Escherichia coli B were markedly less than that of mitomycin C except for benzoyloxymethyl mitomycin C. All of the compounds showed significant activity in vivo against P388 or L1210 leukemia system, and especially benzyloxycarbonyl and benzoyloxymethyl mitomycin C showed equal or superior activity to the parent drug at approximately the same low dose area. These results suggested that most of the compounds exhibit their cytotoxicity against tumor cells after being regenerated to their parent drug in the body.