Development of New Anti-tuberculosis Drug Candidates

Shi, Ruiru; Sugawara, Isamu

doi:10.1620/tjem.221.97

Cited by 23 publications

(28 citation statements)

References 55 publications

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“…Such a search is now in progress in large pharmaceutical companies, including Johnson & Johnson (http://www.jnjru.ru/), Novartis (http://www.novartis.ru/), Eli Lilly (http://www.lilly.ru/Nitro/), etc. A number of new compounds, including those affecting new targets and having new mechanisms of action, have already been put to clinical trials (for a review, see [104][105][106][107][113][114][115][116][117][118][119][120][121]; Table 3). It seems promising for this purpose to study protein kinases, which are numerous enzymes that are involved in the bacterial response to environ mental changes, including phosphorylation reactions.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium tuberculosis mutants with multidrug resistance: History of origin, genetic and molecular mechanisms of resistance, and emerging challenges

2012

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The review summarizes the data on the Mycobacterium tuberculosis mutations that lead to multi drug resistance (MDR) to various antibiotics. MDR strains arose over the past 30 years as a variety of antitu berculosis drugs were introduced in medicine, and they largely discount the results of chemotherapy for tuberculosis. The most dangerous of them are strains with extensive drug resistance (XDR), which are resis tant to four or five different drugs on average. The molecular mechanisms that make a strain resistant are con sidered. XDR and MDR strains result from successive and usually independent resistance mutations, which arise in various regions of the mycobacterial genome. In addition, the formation of resistant strains is affected by the phenomenon of tolerance and mycobacterial latency in infected tissues.

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Section: Discussionmentioning

confidence: 99%

Mycobacterium tuberculosis mutants with multidrug resistance: History of origin, genetic and molecular mechanisms of resistance, and emerging challenges

2012

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“…In these compounds, the authors determined that incorporating a lipophilic component into the nicotinamide hemiamidal framework provides more active derivatives. 89,90 5. Discussion: Tuberculosis (TB) is one of the oldest and most pervasive diseases in history.…”

Section: Isoniazid Analoguesmentioning

confidence: 99%

A Review on Potent Antitubercular Agent Isoniazid and Its Analogues

Asif

2013

Int J Pharmceut Chem

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ABSTRACT:There has been considerable interest in the development of new anti tubercular agents particularly against multidrug resistance and extensively drug resistant strain of tuberculosis because mycobacterium species have developed resistant against currently used drugs. The currently use antitubercular drugs having toxic effect and long period of therapeutic treatment. Therefore, many researchers have synthesized various newer drugs and analogues of currently used drugs for tuberculosis treatment. These observations have been guiding for the development of newer analogues that possess potent antitubercular activity with minimum side effects with effectiveness against multidrug resistant mycobacterium, and also in patient co-infected with HIV/AIDS. In this review we are discussed about isoniazid and it analogues as potent antitubercular agents.

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“…PA 824 is a nitroimidazole derivative that was developed from a series of nitroimidazofurans originally investigated as radio-sensitizers for cancer chemotherapy [38]. The lead compound was found to be mutagenic, but it was found to have significant bactericidal activity against replicating tuberculosis organisms in vitro [39].…”

Section: New Drugsmentioning

confidence: 99%

“…Phase I studies have shown good tolerance among healthy volunteers in doses up to 400 mg with no adverse effects being observed [38]. The initial EBA studies have shown low bactericidal activity during the first 4 days.…”

Section: New Drugsmentioning

confidence: 99%

Antituberculosis therapy for 2012 and beyond

Lauzardo

Peloquin

2012

Expert Opinion on Pharmacotherapy

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Introduction In terms of human suffering, tuberculosis has a huge impact on global society, making it arguably the most important infectious disease in history. Despite the devastating impact on society, the tools to fight tuberculosis are very limited. Current standard therapy has been used for over 40 years and threats, such as the HIV epidemic and drug-resistant strains, undermine efforts to control the disease. New drugs are needed to address the challenges faced globally. Areas covered Current therapy is briefly reviewed in this paper and then new doses and combinations of existing drugs are presented. New candidate drugs are also discussed, along with the potential benefits and pitfalls of each of the compounds and approaches to therapy. Expert opinion Despite the need to develop new drugs, the ability of programs to deliver existing therapies must not be neglected. Directly observed therapy and a standard basic level of care for all patients with tuberculosis, regardless of where they reside, is imperative, and will ensure that new drugs and regimens will have the greatest possible impact. New combination regimens, including PA 824 and TMC207, in combination with existing drugs, are very exciting – not only because of their ability to shorten treatment regimens in pan-susceptible cases, but also because they can be used among drug-resistant strains. Although an effective vaccine will probably be necessary to eliminate tuberculosis, new drugs and combination regimens have the potential to save millions of lives before tuberculosis is finally eliminated.

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Development of New Anti-tuberculosis Drug Candidates

Cited by 23 publications

References 55 publications

Mycobacterium tuberculosis mutants with multidrug resistance: History of origin, genetic and molecular mechanisms of resistance, and emerging challenges

Mycobacterium tuberculosis mutants with multidrug resistance: History of origin, genetic and molecular mechanisms of resistance, and emerging challenges

A Review on Potent Antitubercular Agent Isoniazid and Its Analogues

Antituberculosis therapy for 2012 and beyond

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