Rana Abdelaziz
photo: Rana Abdelaziz May 2020;
source: private
Tuberculosis (TB), which is caused by Mycobacterium tuberculosis (Mtb), is one of the oldest and most pervasive respiratory transmitted diseases in history. According to the WHO, it is one of the top 10 causes of death worldwide. The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mtb strains necessitates the search for new targets and antitubercular agents.
Among new targets, the oxidative phosphorylation pathway in Mtb has gained a lot of attention. This pathway is of particular interest since it is important for the viability of both active and dormant Mtb, and also differs in structure from the mammalian respiratory chain. Thus, drugs targeting this pathway are selective inhibitors as well as likely to shorten the duration of TB treatment.
My work focuses on the development and synthesis of small heterocyclic molecules targeting the oxidative phosphorylation pathway. The studies on their binding and reactive interaction are done in collaboration with Prof. John Rubinstein's lab at the University of Toronto, Canada. Their activity testing against Mtb is a collaboration with the lab of PD Dr. Norbert Reiling, Research Center Borstel.
My chemistry work includes the synthesis of a series of compounds, bearing heterocycles like imidazopyridine, through a 6-step synthetic scheme. Since imidazopyridines are reported to target the oxidative phosphorylation pathway in Mtb, this type of heterocycle is of particular interest. The modifications are designed for the very detailed exploration of the molecular drug-target interaction.