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

Abstract

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 μM) while lower cell death potential with an IC₅₀ value of 822.33 ng mL⁻¹ (0.8 μM) 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 μM). 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.