Development of novel anti-tuberculous agents that target the translation and replication of Mycobacterium tuberculosis

Mycobacterium Tuberculosis (M. tuberculosis) is a pathogenic bacterium and the causative agent of tuberculosis, which infects a third of the world population and kills more than 1.5 million people worldwide every year. One of the main reasons for this mortality rate is the evolution of new M. tuberculosis strains that are resistant to currently available antibiotics and that pose a special global healthcare problem. Since human and bacterial ribosomes are structurally different and humans lack DNA gyrase, both bacterial ribosome and the gyrase are excellent targets for drug development, and drugs targeting these processes would most likely have minimum side effects. We have developed small-molecule inhibitors that target these two targets using our newly developed workflow that combines NMR-fragment screening with virtual screening. My goal in this research thesis was twofold: 1) to develop the workflow for drug design, and thereby 2) to develop small-molecule inhibitors. -- From the abstract.