Editorial [ Hot Topic: Drug-Resistant Tuberculosis - A Challenge in Chemotherapy (Guest Editor: Iwao Ojima) ]

In 1993 the World Health Organization declared tuberculosis a global emergency. Currently, it is estimated that one-third of the World's population are infected with Mycobacterium tuberculosis, the organism that causes TB, and that over two million people die each year from this disease. While 5-10% of those infected will develop active TB infections, this percentage rises dramatically in patients with HIV/AIDS. Indeed, TB is a major opportunistic disease in individuals with HIV/AIDS, accounting for 11% of the AIDS-related deaths worldwide each year. Our ability to combat the spread of TB is hindered by poor patient compliance, the accompanying increase in multi-drug resistant TB strains (MDR-TB) and the strong link between TB and HIV/AIDS. In industrialized countries TB treatment costs around US $2,000 per patient, but rises more than 100-fold to up to US $250,000 per patient with MDR-TB. Chemotherapeutics that are active against MDR-TB would therefore be of tremendous benefit and desperately needed now. These compounds would be expected to have unique mechanisms of action, so that mechanisms of resistance as a result of current drug use would not be expected to impact the mode of action. Consequently, new TB chemotherapeutics are needed that (1) improve compliance by either shortening the total duration of treatment or increasing the time between treatment intervals or both, (2) improve efficacy against MDR strains, and (3) target metabolically altered bacterial populations such as latent TB infections. The Guest Editor organized a symposium on “Drug-Resistant Tuberculosis --- Challenge in Chemotherapy” at the American Chemical Society National Meeting, San Diego, in March 2005, on behalf of the ACS Medicinal Chemistry Division. This symposium summarized the current status and ongoing endeavors in the anti-TB chemotherapeutics research to promote the recognition of this serious problem and stimulate the interest of the medicinal chemist community. Due to the small profit making nature of the traditional anti-TB drugs, major pharmaceutical industries are not working on the anti-TB chemotherapy and chemotherapeutics at present. However, this unfortunate situation should be changed to prevent the outbreak of formidable drug-resistant TB in advanced countries. Following up this ACS Symposium, the Guest Editor assembled leading scientists relevant to drug discovery and medicinal chemistry of new generation anti-TB agents and organized this special issue of the Current Topics in Medicinal Chemistry. This special issue includes a very informative overview by Dr. Barbara Laughon, NIAID, NIH, followed by five articles, representing different approaches to this challenging problem. The Guest Editor would like to thank all authors for their excellent contributions to this special issue and sincerely hopes that this special issue attracts shear interests of medicinal chemists in academia and industry to join the worldwide endeavor to combat against drug-resistant TB.