Cytotoxicity, Hemolytic Toxicity, and Mechanism of Action of Pulsatilla Saponin D and Its Synthetic Derivatives.

ABSTRACT: The strong hemolytic toxicity of pulsatilla saponin D (1, HD₅₀ 6.3 μM) has hampered its clinical development as an injectable anticancer agent. To combat this challenge, 17 new derivatives of 1 with ring C, C-28, or C-3 modifications were synthesized and evaluated for cytotoxicity against several selected human tumor lines, as well as for hemolytic toxicity against rabbit erythrocytes. Structure-activity relationship (SAR) and structure-toxicity relationship (STR) correlations were also elucidated. Compared to the lead compound 1, the hemolytic activity of all 17 derivatives dropped dramatically. Notably, compound 14 exhibited significant cytotoxicity toward A549 human lung cancer cells (IC₅₀ 2.8 μM) in a dose-dependent manner without hemolytic toxicity (HD₅₀

SUBMITTER: Chen Z 

PROVIDER: S-EPMC6448791 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature