Synthesis of hexose-platinum conjugates for cancer treatment | Poster Board #1748

Cisplatin is an essential part of combination chemotherapy to treat cancer. The compounds bind to and crosslink DNA, thus initiating apoptotic pathways in cancer cells. While many patients exhibit high initial responsiveness to treatment, numerous side effects lessen the therapeutic value of this metallodrug.

When cancer cells grow at a high rate, they have an increased energy demand compared to non-cancerous cells; with that they need to facilitate an increased cellular uptake of energy sources, mainly glucose and fructose. Accordingly, many cancer cells overexpress hexose transporters, integral membrane proteins responsible for the transport of hexoses across cellular membranes. To focus the uptake of platinum drugs on fast-growing cells and by that to reduce deleterious side effects due to the interaction of the drugs with biomolecules other than DNA in cancer cells, hexose platinum conjugates that are potential substrates of hexose transporters are being synthesized. The conjugates consist of three domains, namely a transporter substrate, a spacer, and a pharmacophore. A convergent synthetic approach allows to independently vary these domains and to systematically study substrate-transporter and drug-DNA interactions. Several drug candidates have been synthesized and characterized.