Development of 1,3,6-Tribenzoylated Glucose as an Antiausterity Agent Targeting Tumor Microenvironment

One aspect of cancer-specific environments, nutrient starvation, is a factor in cancer cell resistance to treatment with chemotherapeutic agents and development of malignancy. Our newly synthesized novel glu-cose derivative beta-1,3,6-O-tribenzoyl-D-glucose (3) showed preferential cytotoxicity against PANC-1 human pancreatic cancer cells as well as HT-29 human colon cancer cells depending on low nutritional environment. The amount of ester functionalization in 3 is important. None of the mono-and tetrabenzoylated D-glucose analog showed cytotoxicity, and dibenzoylated D-glucoses showed only limited cytotoxicity. Fluorescence im-aging with double staining of Hoechst 33342 and propidium iodide clearly showed that 3 actually causes cell death in a nutrient deprived medium. We thus demonstrate that an inexpensive natural product, D-glucose, is a unique template for attachment of acyl moieties to target tolerance to nutrient starvation. We expect these compounds will lead to additional compounds to treat refractory cancers by diversification of chemically modified glucose.

Automated summary

Nutrient starvation in cancer-specific environments contributes to cancer cell resistance to chemotherapy and malignancy development. Our newly synthesized glucose derivative, beta-1,3,6-O-tribenzoyl-D-glucose (3), exhibits preferential cytotoxicity towards pancreatic and colon cancer cells in low nutritional environments. The extent of ester functionalization in compound 3 plays an important role. Fluorescence imaging confirms that compound 3 induces cell death in nutrient-deprived conditions. This study highlights the potential of chemically modified glucose in developing compounds to treat refractory cancers.