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

Abstract

In order to study the structure-activity relationship (SAR) of C₂₁-steroidal glycosides toward human cancer cell lines and explore more potential anticancer agents, a series of 3β-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 (2k) exhibited the highest antiproliferative activity aganist HepG2 cells with an IC₅₀ 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 C₂₁-steroidal aglycones, and compound 2k represents a potential anticancer agent deserved further investigation.

Keywords: 3β-O-neoglycosides; Anticancer activity; Caudatin; Glycosylated modification.