Silybin or
silibinin, a flavonolignan isolated from Milk thistle seeds, is one of the popular dietary supplements and has been extensively studied for its
antioxidant, hepatoprotective and anti-
cancer properties. We have envisioned that potency of
silybin could be further enhanced through suitable modification/s in its chemical structure. Accordingly, here, we synthesized and characterized a series of
silybin derivatives namely
2,3-dehydrosilybin (DHS), 7-O-methylsilybin (7OM),
7-O-galloylsilybin (7OG), 7,23-disulphatesilybin (DSS), 7-O-palmitoylsilybin (7OP), and 23-O-palmitoylsilybin (23OP); and compared their anti-
cancer efficacy using human
bladder cancer HTB9,
colon cancer HCT116 and prostate
carcinoma PC3 cells. In all the 3 cell lines, DHS, 7OM and 7OG demonstrated better growth inhibitory effects and compared to
silybin, while other
silybin derivatives showed lesser or no efficacy. Next, we prepared the optical isomers (A and B) of
silybin, DHS, 7OM and 7OG, and compared their anti-
cancer efficacy. Isomers of these three
silybin derivatives also showed better efficacy compared with respective
silybin isomers, but in each, there was no clear cut
silybin A versus B isomer activity preference. Further studies in
HTB cells found that DHS, 7OM and 7OG exert better apoptotic activity than
silibinin. Clonogenic assays in HTB9 cells further confirmed that both the racemic mixtures as well as pure optical isomers of DHS, 7OM and 7OG were more effective than
silybin. Overall, these results clearly suggest that the anti-
cancer efficacy of
silybin could be significantly enhanced through structural modifications, and identify strong anti-
cancer efficacy of
silybin derivatives, namely DHS, 7OM, and 7OG, signifying that their efficacy and toxicity should be evaluated in relevant pre-clinical
cancer models in rodents.