Current Status of Some Antituberculosis Drugs and the Development of new Antituberculous Agents with Special Reference to their In Vitro and In Vivo Antimicrobial Activities

Abstract

Tuberculosis (TB) is a growing international health concern, since it is the leading infectious cause of death in the world today. In particular, the increasing prevalence of multidrug-resistant (MDR)-TB has greatly contributed to the increased difficulties in the control of TB. Because of the global health problems of TB, the increasing rate of MDR-TB and the high rate of a co-infection with HIV, the development of potent new anti-TB drugs without cross-resistance with known antimycobacterial agents is urgently needed. This article deals with the following areas. First, it briefly reviews some recent findings on the pharmacological status of fluoroquinolones and rifamycin derivatives. Second, it describes other types of new agents, such as oxazolidinones (linezolid, PNU-100480), nitroimidazoles (nitroimidazopyran PA-824, metronidazole), 2-pyridone, riminophenazines and diarylquinolines, which are being developed as anti-TB drugs. In addition, the future development of new antitubercular drugs is briefly discussed according to the potential pharmacological targets. New critical information on the whole genome of Mycobacterium tuberculosis (MTB) was recently elucidated and increasing knowledge on various mycobacterial virulence genes will promote the progression in the identification of genes that code for new drug targets. Using such findings on MTB genome, drug development using quantitative structure-activity relationship may be possible in the near future.

Potential antimicrobial agents for the treatment of multidrug-resistant tuberculosis

“…Unfortunately, development of new drugs is time-consuming, difficult and expensive, and low-and middle-income countries that comprise 95% of TB cases around the world have limited resources for health expenditure as well as lack of support for research [15]. In order to speed up novel treatments for MDR-TB, in this review, we explore the possibility of expanding the indications of drugs already on the market.…”

Immunotherapeutic efficacy of recombinantMycobacterium smegmatisexpressing Ag85B–ESAT6 fusion protein against persistent tuberculosis infection in mice

“…2 Currently available anti-TB chemotherapy drugs have shown high efficacy for killing most of the actively replicating bacteria within the first few days of a course of treatment, but long-term therapy is still required for a persistent population of slowly replicating or dormant bacilli. 3 However, long-term use of anti-TB drugs has shown significantly induced lung inflammation and pathogenesis of lung diseases. Besides the potential side effects and the associated financial burden, longcourse therapy often results in some unwanted symptoms, such as relapse and drug resistance.…”

Structural view of the regulatory subunit of aspartate kinase from Mycobacterium tuberculosis

“…As one of the most deadly global diseases, tuberculosis (TB) causes about 9 million active infection cases and 2 million casualties every year (Tomioka and Namba, 2006). Although several chemotherapy drugs, including pyrazinamide, ethambutol, isoniazid and rifampicin are clinically effective, the increasing incidences of multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) strains and coinfection of Mtb and human immunodeficiency virus (HIV) have made the control of Mtb more complicated and challenging and the development of novel therapeutic anti-TB drugs in urgent demands (Corbett et al, 2003;Chan and Iseman, 2008).…”