Ottenheijm H C, van den Broek L A
Laboratory of Organic Chemistry, University of Nijmegen, The Netherlands.
Anticancer Drug Des. 1988 Mar;2(4):333-7.
The synthesis of sparsomycin and eight lipophilic analogues is discussed. Sparsomycin, a bacterial metabolite, is a potent inhibitor of protein biosynthesis; in addition it has anti-tumour properties. Structure-activity relationship studies indicate that the anti-tumour activity is a direct consequence of the inhibition of protein synthesis. Two of the analogues show a higher anti-tumour activity in vitro as well as in vivo, and are less toxic to mice than sparsomycin. Finally, some properties of sparsomycin are discussed: the drug potentiates the cytotoxicity of cisplatin and is selectively active on tumour cells without affecting human bone-marrow.
本文讨论了稀疏霉素及其八种亲脂性类似物的合成。稀疏霉素是一种细菌代谢产物，是蛋白质生物合成的强效抑制剂；此外，它还具有抗肿瘤特性。构效关系研究表明，抗肿瘤活性是抑制蛋白质合成的直接结果。其中两种类似物在体外和体内均表现出较高的抗肿瘤活性，且对小鼠的毒性比稀疏霉素小。最后，讨论了稀疏霉素的一些特性：该药物可增强顺铂的细胞毒性，对肿瘤细胞具有选择性活性，而不影响人类骨髓。
