10.1021/jm00355a004
The research focuses on the development and evaluation of analogues of mitomycin C and porfiromycin with substituted ethylamines at position 7. These analogues were synthesized and tested for their antitumor activities against various mouse tumors, including P-388 leukemia, L-1210 leukemia, and B-16 melanoma. The study aimed to identify compounds that are at least as potent as mitomycin C but with reduced leukopenic effects. Key chemicals involved in the research include mitomycin C, porfiromycin, and a variety of ethylamine derivatives such as 2-phenylethylamine, 2-chloroethylamine, 2-hydroxyethylamine, and others with different functional groups at the 2-position of the ethylamine. The analogues were prepared using mitomycin A or N-methyl-mitomycin A as starting materials and various amines for substitution. The synthesized compounds were then purified, characterized, and tested for their biological activities. The results showed that some analogues exhibited better antitumor activity and reduced leukopenia compared to mitomycin C, with notable examples being the mercaptoethylamine analogue (8) and the fluoroethylamine analogue (4). The study also explored structure-activity relationships, finding a limited correlation between the potency of the analogues and their hydrophilicity.
10.1021/jo00295a051
The research focuses on developing a practical method for specifically labeling the α-methyl group of mitomycins with deuterium. Mitomycins, particularly mitomycin C, are potent antitumor antibiotics used in cancer chemotherapy, but their use is limited due to severe side effects. To better understand the pharmacokinetics and mechanism of action of mitomycins, the authors aimed to create a method for selective and effective labeling at a metabolically stable position. They used 7,7-(ethylenedioxy)mitomycin (8) as a starting material, which played a crucial role in the methodology. Through a series of reactions involving phenylselenenyl group introduction, oxidative elimination, and reduction, they successfully synthesized [C6-methyl-2H]mitomycin C (3) and [C6-methyl-2H]mitomycin A (4) with deuterium incorporation confirmed by NMR and mass spectrometry analyses. The developed method is also applicable for synthesizing tritium-labeled mitomycins, which will aid in further pharmacokinetic studies and the development of more effective and less toxic antitumor agents.
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