Targeting Tuberculosis: Novel Scaffolds for Inhibiting Cytochrome Oxidase.

Discovered in the 1920s, cytochrome is a terminal oxidase that has received renewed attention as a drug target since its atomic structure was first determined in 2016. Only found in prokaryotes, we study it here as a drug target for (). Most previous drug discovery efforts toward cytochrome have involved analogues of the canonical substrate quinone, known as Aurachin D. Here, we report six new cytochrome inhibitor scaffolds determined from a computational screen and confirmed on target activity through testing. These scaffolds provide new avenues for lead optimization toward therapeutics.