Approaches to the development of new antituberculosis drugs.

In the last two decades, no new major antituberculosis drug has been developed. Although dramatic improvements in chemotherapy for tuberculosis have been achieved through careful studies of drug regimens, there is still a need for new agents that are highly active. The antimycobacterial drugs used at present in therapy for tuberculosis were obtained by either blind screening or chemical modification of active compounds, with tentative optimization of chemotherapeutic properties. Other approaches based on knowledge of the biochemistry of the mycobacterial cell should be tried. Certain constituents of the cell, such as mycolic acids, arabinogalactan, peptidoglycan, and mycobactins, may represent specific targets for new antituberculosis drugs. Products interfering with the biosynthesis of these mycobacterial constituents can be expected to show specific activity against these microorganisms, with no effect on the normal bacterial flora.