Abstract
Tuberculosis is an infectious disease caused by the bacillus Mycobacterium tuberculosis. The World Health Organization publishes global tuberculosis reports annually in order to provide the latest information in the surveillance of drug resistance. Given the alarming rise of resistance to antitubercular drugs worldwide, finding new cellular targets and developing new analogues or new compounds with greater potency against already known targets are both important aspects in fighting drug-sensitive and drug-resistant M. tuberculosis strains. In this context, the introduction of the phenotypic screens as an efficient tool for the identification of active compounds for tuberculosis drug discovery has improved the possibility to find new effective targets.
With this review we describe the state of art of the currently well validated antitubercular drug targets as well as the advances in discovery of new ones. The main targets will be discussed starting from the oldest such as the enoyl reductase InhA which is constantly repurposed with new inhibitors, through the well assessed targets like the gyrase, the ATP synthetase or the RNA polymerase, up to the hot promiscuous targets decaprenylphosphoryl-Dribose oxidase DprE1 and the mycolic acid transporter MmpL3, or the newly validated and promising targets like the CTP synthetase.
Keywords: Tuberculosis, antitubercular drugs, repurposed targets, promiscuous targets, phenotypic screening, drug design.
Current Medicinal Chemistry
Title:New and Old Hot Drug Targets in Tuberculosis
Volume: 23 Issue: 33
Author(s): Laurent Roberto Chiarelli, Giorgia Mori, Marta Esposito, Beatrice Silvia Orena and Maria Rosalia Pasca
Affiliation:
Keywords: Tuberculosis, antitubercular drugs, repurposed targets, promiscuous targets, phenotypic screening, drug design.
Abstract: Tuberculosis is an infectious disease caused by the bacillus Mycobacterium tuberculosis. The World Health Organization publishes global tuberculosis reports annually in order to provide the latest information in the surveillance of drug resistance. Given the alarming rise of resistance to antitubercular drugs worldwide, finding new cellular targets and developing new analogues or new compounds with greater potency against already known targets are both important aspects in fighting drug-sensitive and drug-resistant M. tuberculosis strains. In this context, the introduction of the phenotypic screens as an efficient tool for the identification of active compounds for tuberculosis drug discovery has improved the possibility to find new effective targets.
With this review we describe the state of art of the currently well validated antitubercular drug targets as well as the advances in discovery of new ones. The main targets will be discussed starting from the oldest such as the enoyl reductase InhA which is constantly repurposed with new inhibitors, through the well assessed targets like the gyrase, the ATP synthetase or the RNA polymerase, up to the hot promiscuous targets decaprenylphosphoryl-Dribose oxidase DprE1 and the mycolic acid transporter MmpL3, or the newly validated and promising targets like the CTP synthetase.
Export Options
About this article
Cite this article as:
Chiarelli Roberto Laurent, Mori Giorgia, Esposito Marta, Orena Silvia Beatrice and Pasca Rosalia Maria, New and Old Hot Drug Targets in Tuberculosis, Current Medicinal Chemistry 2016; 23 (33) . https://dx.doi.org/10.2174/1389557516666160831164925
DOI https://dx.doi.org/10.2174/1389557516666160831164925 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
Microwave and Conventional Method Assisted Synthesis of 2-(substituted) -3-(4-methoxybenzyl) Thiazolidin-4-ones Using ZrOCl2·8H2O as a Catalyst
Current Microwave Chemistry Association of the Clinico-Demographic and Laboratory Profile with Treatment Outcomes in Patients with Drug-Resistant Pulmonary Tuberculosis
Current Respiratory Medicine Reviews Human Tuberculosis. III. Current and Prospective Approaches in Anti-Tubercular Therapy
Current Medicinal Chemistry The Manzamines as an Example of the Unique Structural Classes Available for the Discovery and Optimization of Infectious Disease Controls Based on Marine Natural Products
Current Pharmaceutical Design Synthesis and Anti-onchocercal Activity of Isonicotinoylhydrazones and their Copper(II) and Zinc(II) Complexes
Anti-Infective Agents PCR Designing and Amplification of Partial Hydrogenase Gene from Selected Hydrogen Producing Microorganisms
Current Biotechnology Increased Production of Recombinant O-Phospho-L-Serine Sulfhydrylase from the Hyperthermophilic Archaeon Aeropyrum pernix K1 Using Escherichia coli
Current Biotechnology Editorial: Nanomedicines for the Treatment of Tuberculosis: Role of Nanocarriers and Functional Excipients
Recent Patents on Anti-Infective Drug Discovery The Coronin Family and Human Disease
Current Protein & Peptide Science Towards the Design and Development of Agents with Broad Spectrum Chemotherapeutic Properties for the Effective Treatment of HIV / AIDS
Current Medicinal Chemistry Advances in Mycobacterium tuberculosis Structural Genomics: Investigating Potential Chinks in the Armor of a Deadly Pathogen
Infectious Disorders - Drug Targets Uveitis in Horses, Rats and Man: What Do We Learn from Our Pets?
Current Immunology Reviews (Discontinued) Mathematical Descriptors for the Prediction of Property, Bioactivity, and Toxicity of Chemicals from their Structure: A Chemical-Cum-Biochemical Approach
Current Computer-Aided Drug Design Editorial [Hot Topic: New Developments in Drug and Vaccine Discoveries (Executive Editor: Aldar S. Bourinbaiar)]
Current Pharmaceutical Design Toll-Like Receptors: Role in Inflammation and Commensal Bacteria
Inflammation & Allergy - Drug Targets (Discontinued) Synthesis of Imidazo[1,2-b]pyridazine Comprised Piperazine, Morpholine Derivatives as Potent Antimycobacterial Agents with In Vivo Locomotor Activity
Anti-Infective Agents Vitamin D and Sepsis: From Associations to Causal Connections
Inflammation & Allergy - Drug Targets (Discontinued) Targeting the Histidine Pathway in Mycobacterium tuberculosis
Current Topics in Medicinal Chemistry QSAR Models for Anti-Malarial Activity of 4-Aminoquinolines
Current Computer-Aided Drug Design Increase in the Non-HIV-Related Deaths Among Aids Cases in the HAART Era
Current HIV Research