Isocitrate lyase plays a key role for survival of Mycobacterium tuberculosis in the latent form during a chronic stage of infection.
This enzyme is important for M. tuberculosis during steady stage growth when it converts isocitrate to succinate and glyoxylate.
Then, the glyoxylate is condensed with acetyl-CoA to form malate by malate synthase. The carbon conserving glyoxylate pathway has
not been observed in mammals; therefore, it has been determined as a potential drug target for discovery of a new antituberculosis agent.
Novel active molecules should shorten the duration of therapy, prevent resistance development and eliminate latent disease. The review
summarizes recent progresses in isocitrate lyase inhibitors, overviews structural analogues of several metabolic intermediates (3-
nitropropionate, 3-bromopyruvate, itaconate, itaconic anhydride), peptide inhibitors, and recently developed inhibitors with various
chemical structures. The largest inhibitory activity against isocitrate lyase (IC50 of 0.10 ± 0.01 μM) and concomitantly a significant antimycobacterial
activity has been presented by fluoroquinolone derivative 1-cyclopropyl-7-[3,5-dimethyl-4-(3-nitropropanoyl)piperazin-
1-yl]-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, which has incorporated 3-nitropropionyl group as one of the
structural analogue of succinate, a metabolic intermediate.