Synthesis and cytotoxicity evaluation of 4'-amino-4'-dehydroxyloleandrin derivatives.

A series of C4'-substituted oleandrin analogues were designed, synthesized and evaluated for their cytotoxicity towards human cervical carcinoma cell line (HeLa). The structure-activity relationships (SARs) of these compounds were summarized in this paper, and 4'-α-amino-4'-dehydroxyloleandrin 4a (IC50=21.7nM) and 4'-β-amino-4'-dehydroxyloleandrin 4b (IC50=10.9nM) exhibited stronger cytotoxicity compared with oleandrin (IC50=33.3nM). Furthermore, the cytotoxicity of these two compounds towards another five human cancer cell lines (NCI-H266, A549, Jurkat, HL-60 and PC-3) was also evaluated and the IC50 values of β-amino derivative 4b were approximately 2-3 folds lower than that of oleandrin.