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1 Wiadomości Chemiczne

1 2003

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Tuberkulostatyczne chemioterapeutyki

Nowak K., Suryło P., Kowalski P.

Wiadomości Chemiczne

2003

[Z] 57, 9-10

877--906

At the present time tuberculosis is completely treatable. However, it[MS1] is still a major cause of morbidity and mortality among the poorest people. Tuberculosis is the main source of death from among infectious diseases worldwide. In turn, infectious diseases remain the leading cause of death in the world today, greater than cardiovascular disease or cancer. According to the data provided by World Health Organization (WHO), one-third of the world's population is infected with Mycobacterium tuberculosis. In contrary to general expectation, the incidence of mycobacterial disease has significantly increased since 1990 worldwide. This problem has been aggravated by the human immunodeficiency virus (HIV) pandemia and the recent increase in incidences of microbial resistance to antibiotics. Another problem is the lack of the viable research program to develop the new range of the antituberculosis drugs. Since the mid 90’s no new drugs have been introduced, with the exception of a few minor modifications of existing formulas. This review presents history and current summary of the developments in the application and synthesis of tuberculostatic chemotherapeutics. One of the first type of drugs used were salts of heavy metals, which were discontinued quickly due to the high degree of their toxicity. However pirazinamide(2), introduced in 1936 is still being used today. Modern antituberculosis therapies started in 1944 with the Waksman’s discovery of the streptomycin (12). From among modern drugs the most popular are: PAS (15), INH (18), and EMB (34). Schemes 7, 8 and 14, 15 show the methods of synthesis of these compounds. Similarly, schemes 9?11 show the same for the cycloserine (22) antibiotic, and figures 2, 3 and 4 present the structures of the kanamycin 33 cyclic polipeptide 38 and ansamycin 39 antibiotics. Furthermore, detailed description of the methods of synthesis of fluorochinolones 44, 45 and 46 (introduced in 80’s) can be found in schemes 19, 20 and 22. In this article there is also information about the direction of the new research trends taking place in the field of the new antituberculosis agents.