Iyengar B S, Sami S M, Takahashi T, Sikorski E E, Remers W A, Bradner W T
J Med Chem. 1986 Sep;29(9):1760-4. doi: 10.1021/jm00159a033.
Twenty-three new mitomycin C analogues designed to have increased metal complexing ability were synthesized and tested against P388 leukemia in mice. Their ability to complex Cu(II) was revealed by the shifts in their UV absorption spectra caused by this metal. One analogue was clearly more active than mitomycin C in the antitumor assay and two others had good activity. Correlation between antitumor activity and Cu(II) complexing ability was ambiguous. The most active compounds were either not complexers or they were complexers limited to the 2-(2-pyridyl)alkyl type substituent on N7. A variety of amino acid substituents on N7 showed only weak antitumor activity.
合成了23种旨在提高金属络合能力的新型丝裂霉素C类似物,并在小鼠体内针对P388白血病进行了测试。这种金属引起的紫外吸收光谱变化揭示了它们与铜(II)络合的能力。在抗肿瘤试验中,一种类似物的活性明显高于丝裂霉素C,另外两种具有良好的活性。抗肿瘤活性与铜(II)络合能力之间的相关性不明确。活性最高的化合物要么不是络合剂,要么是仅限于N7上2-(2-吡啶基)烷基型取代基的络合剂。N7上的各种氨基酸取代基仅表现出较弱的抗肿瘤活性。