The lead compound diarylquinoline TMC207 was then subsequently identified as a potent inhibitor of the M. tuberculosis ATP synthase through whole genome sequencing of spontaneous resistant mutants. In addition to the potency of TMC207 against both drug-sensitive and MDR-TB strains, the recent success in Phase II clinical trials places TMC207 as a future front-line anti-tubercular agent. Similarly, the M. tuberculosis inhibitors SQ109 adamantly ureas, and benzimidazole were identified following HTS campaigns and chemical lead optimization. The cellular target of SQ109, adamantly ureas, pyrrole BM212, and benzimidazoles, has recently been identified by whole genome sequencing of spontaneous resistant mutants generated against each inhibitor series, which revealed the common target MmpL3, a membrane transporter involved in the export of trehalose monomycolate and cell wall biosynthesis. Another inhibitor series found to have anti-TB activity are the imidazo pyridine-3-nitroso compounds, but they exhibit undesirable toxicity in a VERO cell line. A similar family of compounds, the imidazo pyridine-3-hydrazones, have been synthesized but are all inactive against M. tuberculosis H37Rv. More recently, 3-amino-imidazo AP24534 pyridines were shown as M. tuberculosis glutamine synthetase inhibitors. The anti-TB properties of the 2,7-dimethylimidazo pyridine-3-carboxamides have also been investigated. These compounds are synthetically tractable, possess druggable properties, and have excellent selective potency against MDR- and XDR-TB. The IP compounds described here have been found to display potent anti-tubercular activity against both M. bovis BCG and M. tuberculosis. Furthermore the target of these inhibitors has been identified as the b subunit of the cytochrome bc1 complex encoded by the gene qcrB. The cytochrome bc1 complex or complex III of the electron transport chain is an integral membrane protein that forms a key component in the bacterial respiratory system. The complex functions as a ubiquinol-cytochrome C reductase, utilizing a catalytic core of three highly conserved components namely the cytochrome c1, cytochrome b and the Rieske iron sulfur protein. A Q-cycle mechanism couples electron transfer to proton translocation, adding to the proton electrochemical gradient that is used to generate adenosine triphosphate. The mechanism of electron transfer within the cytochrome bc1 complex has previously been described. There are a number of well-characterized inhibitors of the bc1 complex. The elucidation of their mechanism and crystallographic data identifying binding sites has lead to the development of compounds that inhibit the CT99021 function of the cytochrome bc1 complex for therapeutic purposes. These inhibitors tend to target the two catalytic domains utilizing an analogous structure to either quinone or quinol. von Jagow and colleagues first characterized the most widely understood inhibitor of the cytochrome bc1 complex, myxothiazol, an antibiotic from Myxococcus fulvus.