The recrudescence of tuberculosis and related mycobacterial diseases coupled with the rise of AIDS presents many difficult problems for society. TB is now often rapidly fatal and is more difficult to control as the strains now are often multiresistant to the drugs normally used for their control. Among the more likely sources of weapons to use in this crisis is the discovery of novel antimycobacterial agents. Using directed screening methods, the applicant has identified higher plant extracts that contain antimycobacterial agents whose structures are novel and comparatively simple, and convenient chemical synthesis has led to a number of analogs with significant activity against multiresistant clinical strains and a number of other, diverse, structural types are advancing toward similar testing. A large number of extracts that have shown in vitro activity against M. smegmatis, M. tuberculosis and M. avium complex in preliminary studies await analysis. The ultimate objective of this proposal is to discover novel potential chemotherapeutic agents for the treatment of mycobacterial infections and to advance them by logical stages into the clinic.
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