Rational approach in the new antituberculosis agent design: inhibitors of InhA, the enoyl-ACP reductase from Mycobacterium tuberculosis

In conjunction with the spread of HIV infection, tuberculosis (TB) has been among the worldwide health threats. Mycobacteria resistance to the drugs currently used in the therapeutics is the main cause of TB resurgence. In view of this severe situation, the new and selective anti-TB design is of utmost importance. Fatty acid biosynthesis is a prokariontes and eucariontes biochemical process that supplies essential precursors for the assembly of important cellular components, such As phospholipids, lipoproteins, lipopolysaccharides, mycolic acids and cellular envelope. However; the biochemical and functional differences between the bacterial and mammals fatty, acid synthetic path way have endowed the mycobacterial enzymes with distinct properties. These provide valuable opportunities structure- or catalytic mechanism-based design of selective inhibitors as novel anti-TB drugs with improved properties. The enoyl-reductases are essential enzymes in the fatty acids elongation pathway towards the mycolic acids, the main micobacteria cell wall constituents, biosynthyesis and so they are potential targets to the rational new antimycobacteria drug design. This paper highlights recent approaches regarding the design of new anti-TB agents, particularly the enoyl-ACP reductase inhibitors.