Identification of inhibitors targeting Mycobacterium tuberculosis cell wall biosynthesis via dynamic combinatorial chemistry

In this study, we report a dynamic combinatorial approach along
with highly efficient in situ screening to identify inhibitors of UDPgalactopyranose
mutase (UGM), an essential enzyme involved
in mycobacterial cell wall biosynthesis. These two technologies
converged to the identification of a new UGM inhibitor chemotype.
Importantly, the best molecule not only displayed high affinity for the
target enzyme but also exhibited in vitro growth inhibition against whole
Mycobacterium tuberculosis cells. The strategy described here provides
an avenue to explore a novel inhibitor class for UGMs and paves the way
for further pharmacological studies on tuberculosis treatment.