Titre : Synthesis of Conformationally-Controlled Polycycles for Use as Enzyme Inhibitor Scaffolds: a Case Study in the Engineering of Novel Sialidase Inhibitors for Influenza and Cancer Treatment.
La conférence sera prononcée (en anglais) par le professeur Jeremy Wulff, du département de chimie de l'University of Victoria.
Résumé : Conformational control of large inhibitors (for example by macrocyclization) is often found to improve potency and reduce off-target binding. In principle, internal rigidification of small molecule inhibitors should provide similar benefits, but for various reasons this is less commonly practiced in the pharmaceutical industry. In an academic setting, however, this strategy has the potential to lead to more structurally-interesting targets (fun!) that come with a number of improved pharmaceutical properties (useful!).
In this presentation, we will describe a novel route to a growing family of conformationally-controlled bicyclic and tricyclic sulfones, as well as the application of those scaffolds to the creation of enzyme inhibitors that address a key conformational problem in the field of influenza treatment. We will also present some very recent (and still not well understood) data on the application of these inhibitors to the problem of selective sialidase inhibition in cancer, where we have identified one compound that reversibly – and completely! – blocks the migration of prostate cancer cells. This marks the first time that a small molecule sialidase inhibitor has been shown to affect cancer cell motility, and opens the door to new families of chemotherapeutics.