Vloon W J, Kruk C, Pandit U K, Hofs H P, McVie J G
J Med Chem. 1987 Jan;30(1):20-4. doi: 10.1021/jm00384a003.
New side-chain-modified bleomycins (BLMs) 3a-k have been synthesized by the reaction of demethyl BLM A2 with alpha-bromoacetamides (2a-k). The structures of these BLM analogues have been established by comparison of their NMR spectra with the corresponding spectra of model thiazole derivatives. Mass spectra (FAB) of the modified BLMs are not informative, since the fragmentation patterns exhibit a loss of the modified chain moiety, presumably in the matrix. The purity of the compounds is attested by TLC and HPLC analyses. Biological evaluation of 3a-k in in vitro (survival of B16 melanoma cells) shows that the compounds are almost as effective as bleomycin. Examination of the effects of 3c, 3e, and 3f on lungs of male mice indicates that the analogues do not exhibit lower pulmonary toxicity than bleomycin.
通过去甲基博来霉素A2与α-溴代乙酰胺（2a-k）反应合成了新的侧链修饰博来霉素（BLMs）3a-k。通过将这些BLM类似物的核磁共振谱与相应的噻唑衍生物模型谱进行比较，确定了它们的结构。修饰后的博来霉素的质谱（快原子轰击）信息不足，因为碎裂模式显示修饰链部分丢失，可能是在基质中。通过薄层色谱法和高效液相色谱分析证实了化合物的纯度。对3a-k进行体外生物学评估（B16黑色素瘤细胞存活情况）表明，这些化合物的效果几乎与博来霉素一样好。对3c、3e和3f对雄性小鼠肺部影响的研究表明，这些类似物的肺部毒性并不低于博来霉素。
