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A series of ester and amide derivatives of triterpenoid saponin  Pulsatilla  saponin D (PSD) were designed, synthesized, and evaluated for their antiproliferative activity. Compounds 1 and 6 displayed 1.7–8.3 times more potent cytotoxicity (IC 50  = 1.2–4.7 and 1.7–4.5 μM, respectively) against five human tumor cell lines (SMMC-7721, MCF-7, NCI-H460, A549, and HCT-116)  in vitro  and lower acute toxicity to mice  in vivo  than did PSD. Furthermore, compound 6 was observed to show potent tumor growth inhibition against mice H22 hepatocellular cells (49.8% at 20 mg/kg) and induce cell cycle at G 1  phase and apoptosis in HCT-116 cells.

Synthesis, Biological Evaluation, and Mode of Action of Pulsatilla Saponin D Derivatives as Promising Anticancer Agents