Synthesis and anticancer properties of dendritic glycoconjugates containing multiple o-carborane clusters

Boron-rich glycodendrimers containing three to six peripheral hydrophilic glucose moieties and three ortho-carborane clusters have been synthesized. Adding more number of glucose moieties compensated the hydrophobicity of ortho-carboranes and made the glycodendrimers completely water soluble. In vitro cytotoxicity of the synthesized glycodendrimers 16, 18 and 20 has been evaluated against MCF-7 breast cancer cell lines and compared with that of the core compound 7 without any peripheral glucose moieties. The glycodendrimer 20 having nine glucose moieties has shown the highest cell death potential with an IC50 value of 41.35 ng mL(-1) (0.01 mu M) while lower cell death potential with an IC50 value of 822.33 ng mL(-1) (0.8 mu M) has been observed in the case of compound 7. The cytotoxicity of glycodendrimer 20 was found to be 600 times higher than the cytotoxicity of the chemotherapeutic drug cisplatin (IC50 6 mu M). The study of caspase-3 activity reveals that compounds 7, 16, 18 and 20 induce cell death in MCF-7 cell lines via apoptosis. The results indicate that the glycodendrimers containing multiple o-carborane clusters could be useful tumor specific anticancer agents.

Automated summary

Boron-rich glycodendrimers containing multiple glucose moieties and ortho-carborane clusters were synthesized and found to be completely water soluble due to increased hydrophilicity. In vitro evaluation showed that the glycodendrimer with nine glucose moieties exhibited the highest cytotoxicity against MCF-7 breast cancer cells, with a 600-fold higher potency than cisplatin. The study suggests that these glycodendrimers could serve as tumor-specific anticancer agents.