Discovery of novel inhibitors targeting the mycobacterial cell wall

Promoter

Prof. Stéphane VINCENT, UNamur, Laboratory of Bio-Organic Chemistry (CBO)

Jury

Richard DANIELLOU (Université d'Orléans), Yongmin ZHANG (Université Pierre et Marie Curie), Weidong PAN (Key laboratory of chemistry for natural products of Guizhou province and chinese academy of sciences), Steve LANNERS, président (UNamur), Stéphane VINCENT, promoteur (UNamur)

Summary

Twenty years after the WHO declared TB disease to be a global public health emergency, limited progress has been made on curbing, let alone eradicating, the TB epidemic. In 2015, there were an estimated 10.4 million incident cases of tuberculosis (TB), and an estimated of TB incidence have been revised upwards for the period 2000–2015. In an attempt to combat the global TB epidemic, there has been extensive research into the development of novel vaccines and chemotherapeutics against TB. With the emergence of multidrug resistant (MDR) and extensively drug resistant (XDR) TB, leading the current drugs lose efficiency. Therefore the desperate need for antibiotics with novel mechanisms of action remains.

Among the different enzymes involved in the formation of the mycobacterial cell wall, UDP-Galactopyranose mutase (UGM) was identified as a new target. Indeed, this enzyme allows a peculiar reaction: the contraction of the cycle of UDP-Galp into UDP-Galf. This thesis was based on the identification of novel potential inhibitors of UGM in order to understand the mechanism of this enzyme. The enzymatic studies were performed on two different categories of molecules: synthetic compounds and natural products.