Bielefeld University, Department of Chemistry, Organic and Bioorganic Chemistry, Universitatsstrasse 25, 33615 Bielefeld, Germany.
Org Lett. 2010 Mar 5;12(5):1064-7. doi: 10.1021/ol1000473.
An endocyclic trans-amide linkage within the macrocyclic antitumor agent cryptophycin-52 was replaced by a 1,4-disubstituted 1H-1,2,3-triazole ring. Macrocyclisation of the triazole analogue was accomplished by macrolactamization as well as by Cu(I)-mediated "click"-cyclization. Compared to cryptophycin-52, in vitro cytotoxicity of "clicktophycin-52" against the multidrug resistant human cancer cell line KB-V1 is only slightly reduced.
在大环抗肿瘤药物隐色霉素-52 内的中环反酰胺键被 1,4-取代的 1H-1,2,3-三唑环取代。三唑类似物的环化通过大环内酯化以及 Cu(I)介导的“点击”环化来实现。与隐色霉素-52 相比，“点击隐色霉素-52”对多药耐药的人癌细胞系 KB-V1 的体外细胞毒性仅略有降低。
