Structure-guided design of new antibacterial agents against dormant Mycobacterium tuberculosis

Important results from the project

The overall objectives of this proposal are to further develop the design of inhibitors of mycobacterial enzymes, building on and exploiting the key discoveries from the previous period. Focus of the project are on selected enzymes from cysteine biosynthesis and cell wall remodeling in Mycobacterium tuberculosis. All milestones and deliverables outlined in the proposal have been achieved in the course of the project.

Expected long term effects

The project has led to the discovery of new small compounds with high potency as inhibitors of our target proteins, particularly against CysM, an enzyme from the biosynthetic pathway of the essential amino acid cysteine in M. tuberculosis. The increase in antibiotic resistence in M. tuberculosis makes the treatment of this disease increasingly more difficult. The project has identified new small molecules that could provide the starting point for the development of new antibiotics against this pathogen.

Approach and implementation

The development of new inhibitors was based on the knowledge of the three-dimensional structures of proteins that were identified as essential for growth/survival of the pathogen in infected host cells. The project was built on the expertise of the Indian research team in medicinal chemistry and drug development and the knowledge in structural biology, enzymology and molecular biology of the Swedish team.