Structure-Activity Relationships of Novel Pyrimidine Derivatives as potential antimycobacterial Agents

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains the leading cause of death from a single infectious agent, exerting severe health and economic burdens, particularly in Sub-Saharan Africa and South-East Asia. When investigating the mechanism of action, we initially focused on DprE1 - the validated target of the parent purine derivatives. However, the scaffold simplification appeared to alter the mode of action, and current data suggest that inhibition of the essential transporter MmpL3 is the most probable mechanism.