Preparation of dendritic carboranyl glycoconjugates as potential anticancer therapeutics

A series of carborane-appended glycoconjugates containing three and six glucose and galactose moieties have been synthesized via Cu(i)-catalyzed azide-alkyne [3 + 2] click cycloaddition reaction. The carboranyl glycoconjugates containing three glucose and galactose moieties were found to be partially water soluble whereas increasing the number to six made them completely water soluble. The evaluation of cytotoxicities and IC₅₀ values of newly synthesized carboranyl glycoconjugates was carried out using two cancerous cell lines (MCF-7 breast cancer cells and A431 skin cancer cells) and one normal cell line (HaCaT skin epidermal cell line). All carboranyl glycoconjugates showed higher cytotoxicities towards cancerous cell lines than the normal cell line. Carboranyl glycoconjugates containing three glucose and galactose moieties (compounds 15 and 17) were found to be more cytotoxic than the glycoconjugates containing six glucose and galactose moieties (compounds 19 and 21). Moreover, administration of 100 μM concentrations of compounds 15 and 17 inhibited up to 83% of MCF-7 breast cancer cells and up to 79% A431 skin cancer cells. However, administration of similar concentrations of carboranyl glycoconjugates could inhibit only up to 35-45% of HaCaT normal epidermal cells. Thus, due to the higher cytotoxicities of dendritic carboranyl glycoconjugates towards cancer cells over healthy cells, they could potentially be useful for bimodal treatment of cancer such as chemotherapy agents and boron neutron capture therapy (BNCT) agents as well.