Synthesis and biological evaluation of 3β-O-neoglycosides of caudatin and its analogues as potential anticancer agents

In order to study the structure–activity relationship (SAR) of C 21 -steroidal glycosides toward human cancer cell lines and explore more potential anticancer agents, a series of 3 β -O-neoglycosides of caudatin and its analogues were synthesized. The results revealed that most of peracetylated 3β-O-monoglycosides demonstrated moderate to significant antiproliferative activities against four human cancer cell lines (MCF-7, HCT-116, HeLa, and HepG2). Among them, 3β-O-(2,3,4-tri-O-acetyl-β-L-glucopyranosyl)-caudatin ( 2 k ) exhibited the highest antiproliferative activity aganist HepG2 cells with an IC 50 value of 3.11 μM. Mechanical studies showed that compound 2k induced both apoptosis and cell cycle arrest at S phase in a dose dependent manner. Overall, these present findings suggested that glycosylation is a promising scaffold to improve anticancer activity for naturally occurring C 21 -steroidal aglycones, and compound 2 k represents a potential anticancer agent deserved further investigation.