Fighting tuberculosis: An old disease with new challenges (original) (raw)
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Challenges in the development of drugs for the treatment of tuberculosis
The Brazilian Journal of Infectious Diseases, 2013
Tuberculosis infection is a serious human health threat and the early 21st century has seen a remarkable increase in global tuberculosis activity. The pathogen responsible for tuberculosis is Mycobacterium tuberculosis, which adopts diverse strategies in order to survive in a variety of host lesions. These survival mechanisms make the pathogen resistant to currently available drugs, a major contributing factor in the failure to control the spread of tuberculosis. Multiple drugs are available for clinical use and several potential compounds are being screened, synthesized, or evaluated in preclinical or clinical studies. Lasting and effective achievements in the development of anti-tuberculosis drugs will depend largely on the proper understanding of the complex interactions between the pathogen and its human host. Ample evidence exists to explain the characteristics of tuberculosis. In this study, we highlighted the challenges for the development of novel drugs with potent bacteriostatic or bactericidal activity, which reduce the minimum time required to cure tuberculosis infection. (Y.S. Lee). exceeding 5% per year. 1 However, surveillance and mathematical modeling suggests that the total TB incidence per capita is falling at an estimated 1% per year, a finding that indicates that the global incidence rate will decrease by 2015. However, the world's population is growing at about 2% per year, and thus the total number of new TB cases remains on the rise. 2 This finding reveals the relative failure of the existing management strategies for TB and the inadequate effectiveness of public health systems, mainly in underdeveloped countries. In spite of the availability of anti-TB drugs developed over the last five decades, one-third of the world's population retains a 1413-8670/$ -see front matter
2017
Tuberculosis is a major health problem, which is not only fatal, if left untreated; but also spreads rapidly and is persistent in nature. This makes it one of the world's deadliest diseases. There is a recorded history describing prevalence of TB-like symptoms since ancient times. During 1980s, the disease became more widespread due to the upsurge of HIV infection, which renders the individual immune-compromised, and hence more prone to Mycobacterium tuberculosis bacilli infection. While the scientific world battled with the Mycobacterium persistence and latency, MDR forms appeared making the challenge for eradicating TB, all the more complex and arduous to achieve. Indian scriptures, especially the Vedas, are rich sources of information on plant based medicinal products with amazing efficacy to cure various diseases, including TB. This area remains largely unexplored. The present review discusses a general outline of the disease, drugs currently used for the treatment, new drug...
Current development and future prospects in chemotherapy of tuberculosis
Respirology, 2010
Novel chemotherapeutic drugs are needed to improve tuberculosis (TB) control, especially in the developing world. Given the magnitude of the problem and the resources available in countries that have the highest burden of disease, the present standards of care for the treatment of drug-susceptible TB, drug-resistant TB, TB/human immunodeficiency virus (HIV) coinfection, and latent TB infection are all unsatisfactory. Because no truly novel compounds for the treatment of TB have been discovered in the past 40 years, the recent enhanced activity in the research and development of new TB drugs is extremely encouraging. Seven compounds are presently in clinical development specifically for the treatment of TB. Other known antibiotic compound families are being investigated preclinically, in an attempt to identify new antimicrobial drugs with specific antituberculous activity. In addition, novel targets have been identified and are the subject of efforts to validate their potential usefulness in the treatment of TB. q32 q33 q34 q35 q36 q37 q38
Novel targets for tuberculosis drug discovery
Current opinion in pharmacology, 2006
Since the determination of the Mycobacterium tuberculosis genome sequence, various groups have used the genomic information to identify and validate targets as the basis for the development of new anti-tuberculosis agents. Validation might include many components: demonstration of the biochemical activity of the enzyme, determination of its crystal structure in complex with an inhibitor or a substrate, confirmation of essentiality, and the identification of potent growth inhibitors either in vitro or in an infection model. If novel target validation and subsequent inhibition are matched by an improved understanding of disease biology, then new antibiotics could have the potential to shorten the duration of therapy, prevent resistance development and eliminate latent disease.
Attack on the Scourge of Tuberculosis: Patented Drug Targets
Recent Patents on Anti-Infective Drug Discovery, 2006
Tuberculosis is one of the most devastating bacterial diseases, with increasing rates of morbidity and mortality, despite the presence of effective chemotherapy and Bacillus-Calmette-Guerin (BCG) vaccine. The success of Mycobacterium tuberculosis lies in its ability to spread by aerosol droplets, evade the host immune system and to persist in pulmonary granulomas. The advancement in the field of molecular and cellular microbiology and the availability of transcriptome and proteome data of M. tuberculosis have aided in understanding the pathogenesis of this organism for developing more effective drugs. The current strategy of drug design is to identify gene products, which are essential for survival and virulence. To date, several gene products of mycobacteria, ranging from proteins involved in cell wall synthesis to energy generation and from entry into host to persistence, have been shown to be essential for the survival or virulence of M. tuberculosis. These proteins and their associated pathways are considered as promising drug targets against M. tuberculosis and several of these have been patent protected. Herein, we enlist drug targets against M. tuberculosis for which patents have been filed and issued during the last ten years. The significance of these drug targets in the development of drug is also discussed. This review presents a comprehensive account of the pivotal information for drug discovery and drug design to all researchers involved in tuberculosis research.
Challenges in Drug Discovery against Tuberculosis
Molecular Epidemiology Study of Mycobacterium Tuberculosis Complex, 2021
Tuberculosis (TB) is one of the deadly diseases in the present era caused by Mycobacterium tuberculosis. Principally, this bacterium attacks the lungs, however, MTB Has been observed affecting any part of the human body including the kidney, spine, and brain. Drug-resistant progression and other associated properties of MTB become a major hurdle in drug discovery to fight against tuberculosis. Moreover, some of the challenging situations such as the low range of chemical agents, the time-consuming process of drug development, the shortage of predictive animal models, and inadequate information of the physicochemical evidence required for effective bacterial penetration, are additional hindrances for the pharmaceutical scientist. In the current chapter, we focus on challenges encountered during drug discovery and need to be overcome as M. tuberculosis has a substantial barrier in its lipid-containing cell wall to inhibit the influx of drugs which is the initial requirement of the dru...
The Medicinal Chemistry of Tuberculosis Chemotherapy
Topics in Medicinal Chemistry, 2011
The development of effective chemotherapy for the treatment of tuberculosis (TB) began in the 1940s and has been reinvigorated recently due to concern regarding the emergence of highly drug-resistant TB strains. This chapter explores the medicinal chemistry efforts that gave rise to current frontline and second-line drugs in global use today and attempts to comprehensively summarize ongoing discovery and lead optimization programs being conducted in both the private and the public sector. TB has a large number of disease-specific considerations and constraints that introduce significant complexity in drug discovery efforts. Conceptually, the disease encompasses all the drug discovery challenges of both infectious diseases and oncology, and integrating these considerations into programs that often demand collaboration between industry and academia is both challenging and rewarding.
Targeting and Synthesizing new Anti-Tuberculosis Agents for use as Drugs
2013
Tuberculosis (TB) is a deadly contagious disease that is caused by a bacterium called Mycobacterium tuberculosis. More than sixty years ago, the introduction of the first anti-TB drugs for the treatment of TB (streptomycin (STR), p-aminosalcylic acid (PAS), isoniazid (INH) and then later ethambutol (EMB) and rifampicin (RIF)) gave optimism to the medical community, and it was believed that the disease would be completely eradicated soon. Recently, highly drug-resistant forms of TB have emerged worldwide. The prolonged use of classical drugs developed a growing resistance and these drugs have gradually become less effective and incapable to meet the challenges, especially those of multi drug resistant(MDR)-TB, Extensively drug resistant(XDR)-TB, and HIV-TB co-infections.This paper attempts to bring out the review of anti-TB drugs, and presents a novel method of synthesizing new anti-tuberculosis drugs and potential compounds to overcome the bacterial resistance and combat the re-emer...