Abstract
Tuberculosis is a major global health problem. In the middle of the last century several laboratories identified, developed and synthesized several substances which were active against Mycobacterium tuberculosis, the causative agent of the disease. In the 1980s the standard oral treatment regimen was introduced with isoniazid, rifampicin, pyrazinamide, and ethambutol. In combination with the DOTS strategy it was possible treat TB within 6–8 months. But with the emergence of drug resistant strains, the formerly successful regiment became ineffective for MDR and XDR TB patients. Even more alarming, the rapidly increasing HIV epidemic also increases the number of HIV-related TB. Facing these facts, it became evident that novel strategies and antibiotics were needed to treat the new forms of TB. But over the last 60 years no novel TB drug was developed or even in the drug pipeline.
But during the last ten years several novel substances have been developed to combat the deadly disease. For the first time in decades the TB drug pipeline is filled again with several promising compounds and many of them have reached Phase II and Phase III clinical trials.
Several laboratories and companies all over the world currently are developing and evaluating these substances. This review presents novel substances, which were for the first time exclusively developed for TB such as bedaquilines, nitroimidazoles and the diamine SQ109. We also summarize the present knowledge about enzymes and biosynthesis pathways which offer potential targets for drug discovery against M. tuberculosis.
Keywords: Bedaquiline, benzothiazinones, drug development, fluoroquinolones, Mycobacterium tuberculosis, nitroimidazoles, oxazolidinones, rifamycin.
Current Topics in Medicinal Chemistry
Title:Filling the Pipeline - New Drugs for an Old Disease
Volume: 14 Issue: 1
Author(s): Matthias Stehr, Ayssar A. Elamin and Mahavir Singh
Affiliation:
Keywords: Bedaquiline, benzothiazinones, drug development, fluoroquinolones, Mycobacterium tuberculosis, nitroimidazoles, oxazolidinones, rifamycin.
Abstract: Tuberculosis is a major global health problem. In the middle of the last century several laboratories identified, developed and synthesized several substances which were active against Mycobacterium tuberculosis, the causative agent of the disease. In the 1980s the standard oral treatment regimen was introduced with isoniazid, rifampicin, pyrazinamide, and ethambutol. In combination with the DOTS strategy it was possible treat TB within 6–8 months. But with the emergence of drug resistant strains, the formerly successful regiment became ineffective for MDR and XDR TB patients. Even more alarming, the rapidly increasing HIV epidemic also increases the number of HIV-related TB. Facing these facts, it became evident that novel strategies and antibiotics were needed to treat the new forms of TB. But over the last 60 years no novel TB drug was developed or even in the drug pipeline.
But during the last ten years several novel substances have been developed to combat the deadly disease. For the first time in decades the TB drug pipeline is filled again with several promising compounds and many of them have reached Phase II and Phase III clinical trials.
Several laboratories and companies all over the world currently are developing and evaluating these substances. This review presents novel substances, which were for the first time exclusively developed for TB such as bedaquilines, nitroimidazoles and the diamine SQ109. We also summarize the present knowledge about enzymes and biosynthesis pathways which offer potential targets for drug discovery against M. tuberculosis.
Export Options
About this article
Cite this article as:
Stehr Matthias, Elamin A. Ayssar and Singh Mahavir, Filling the Pipeline - New Drugs for an Old Disease, Current Topics in Medicinal Chemistry 2014; 14 (1) . https://dx.doi.org/10.2174/1568026613666131113152908
DOI https://dx.doi.org/10.2174/1568026613666131113152908 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Bioactivity of American Ginseng by Knockout Extract Preparation Using Monoclonal Antibody
Current Drug Discovery Technologies Development and Validation of a Rapid and Sensitive Assay for Simultaneous Quantification of Lenalidomide and Dexamethasone in Human Plasma by Liquid Chromatography Coupled to Tandem Mass-Spectrometry
Current Pharmaceutical Analysis New Technologies in Male Contraception
Current Women`s Health Reviews Targeted Inhibition of Rictor/mTORC2 in Cancer Treatment: A New Era after Rapamycin
Current Cancer Drug Targets Regulation of Tumor-Stromal Fibroblast Interactions: Implications in Anticancer Therapy
Current Medicinal Chemistry Screening Novel SAHA Derivatives as Anti-lung Carcinoma Agents: Synthesis, Biological Evaluation, Docking Studies and Further Mechanism Research between Apoptosis and Autophagyetween Apoptosis and Autophagy
Anti-Cancer Agents in Medicinal Chemistry Calcium Metabolism & Hypercalcemia in Adults
Current Medicinal Chemistry Dietary Assumption of Plant Polyphenols and Prevention of Allergy
Current Pharmaceutical Design Exosomes: A Promising Factor Involved in Cancer Hypoxic Microenvironments
Current Medicinal Chemistry Deep Venous Thrombosis Associated with Thalidomide use in a Case of Steroid Dependent Erythema Nodosum Leprosum-a Management Conundrum
Current Drug Safety Inhibition of Akt/mTOR Signaling by the Dietary Flavonoid Fisetin
Anti-Cancer Agents in Medicinal Chemistry Development of WT1 Peptide Cancer Vaccine Against Hematopoietic Malignancies and Solid Cancers
Current Medicinal Chemistry The Clinical Application of Circulating Tumor Cells and DNAs as Prognostic and Predictive Biomarkers in Gastrointestinal Cancer
Current Cancer Drug Targets Monitoring Molecular, Functional and Morphologic Aspects of Bone Metastases Using Non-Invasive Imaging
Current Pharmaceutical Biotechnology Strategies for Detecting Genomic DNA Methylation: A Survey of US Patents
Recent Patents on DNA & Gene Sequences Anti-Angiogenic Therapy: Strategies to Develop Potent VEGFR-2 Tyrosine Kinase Inhibitors and Future Prospect
Current Medicinal Chemistry Proteasome Inhibition: A Promising Strategy for Treating Cancer, but What About Neurotoxicity?
Current Medicinal Chemistry Targeting Heat Shock Proteins 70/90 and Proteasome for Cancer Therapy
Current Medicinal Chemistry Advancement and Strategies for the Development of Peptide-drug Conjugates: Pharmacokinetic Modulation, Role and Clinical Evidence against Cancer Management
Current Cancer Drug Targets Gene therapy for Multiple Myeloma
Current Gene Therapy