Design and Synthesis of Antifungal Drugs

Fungal infections occur when fungus invades the tissue, which can grow and affect the whole body if left untreated. The current antifungal drugs on the market often come with unwanted side effects, and drug resistance will always be a problem. This leads to the necessity for new pathways for inhibiting fungal infections. To this end, we are developing a library of new antifungal agents. An enzyme critical for life, methionine synthase, has a key difference between fungi and humans that can be exploited. An inhibitory molecule can be made to selectively target fungal methionine synthase based on this difference. Utilizing the modelling software Autodock, molecular modelling was done to develop theoretical molecules that target the fungal enzyme. Based on the theoretical modelling, a library of potential inhibitors was synthesized. These compounds were tested in an assay measuring the activity of the fungal enzyme in the presence of our compounds. To further evaluate the activity of each inhibitor, they are tested in a fungal growth assay which show zones of inhibition that prove our molecules are biologically active against fungi.