Antitubercular drugs medicinal chemistry
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ABSTRACT: Tuberculosis (TB) is an ancient disease that has caused inestimable suffering and claimed millions of lives over the centuries. Resistant strains of Mycobacterium tuberculosis have slowly emerged especially in developing countries due to the lack of health care organisation in order to provide the long and costly treatment adapted to patients. In fact, 90% of all TB cases occur in the developing world. People with HIV/AIDS are especially susceptible to tuberculosis due to lack of immune system.Tuberculosis has been treated with combination therapy for over fifty years. Drugs are not used singly (except in latent TB or chemoprophylaxis), and regimens that use only single drug result in the rapid development of resistance and treatment failure.
Keywords:
HIV,Mycobacterium tuberculosis, Multidrug resistant tuberculosis, Extensively drug resistant tuberculosis
INTRODUCTION: Tuberculosis (TB), an airborne infectious disease caused predominantly by Mycobacterium tuberculosis (Mtb), is a global health problem and a leading cause of death among adults in the developing world.
According to the World Health Organization (WHO), one third of the world’s population is infected with Mycobacterium tuberculosis (Mtb). In 2008, there were an estimated about 9.4 million incident cases of TB, 11.1 million prevalent cases of TB, 1.3 million deaths from TB among HIV-negative people and an additional 0.52 million TB deaths among HIV-positive people 1.
Owing to population growth, the number of new cases arising each year is increasing globally, posing a continued health and financial burden in various parts of the world, particularly Asia and Africa. When coupled with the emergence of multidrug-resistant strains of Mycobacterium tuberculosis (MDR-TB),the scale of the problem becomes clear, as it will inevitably become even more difficult to treat TB in the future. It is now more than a decade since the World Health Organization declared TB “a global health emergency” 2.
Treatment of tuberculosis is protracted and burdensome. Tuberculosis control is further complicated by the synergy between tuberculosis and HIV/AIDS and by the development of multi-drug resistant tuberculosis (MDR-TB), which can be defined as strains that are resistance to at least isoniazid and rifampicin, important first line drugs used in TB treatment 3.
Another serious problem, in the context of MDR-TB, is the XDR-TB [abbreviation for extensively drug-resistant tuberculosis (TB), defined as multidrug- resistant tuberculosis plus resistance to a fluoroquinolone and an injectable second-line drug (capreomycin, kanamycin, or amikacin)], has recently emerged as a public health threat.4 Furthermore, common HIV/AIDS anti-retroviral therapies are not compatible with the current TB regimen because of shared drug toxicities and drug interactions, for example, as a consequence of rifampicin-induced cytochrome P450 activation 5. This has spurred new efforts to find new anti-tuberculosis drug candidat