Abstract
Several groups working in the field of the development of new antituberculosis drugs have recently reported active compounds targeting mycobacterial enzyme DprE1. Along with its counterpart, DprE2, it catalyses a unique epimerization reaction resulting in the synthesis of decaprenylphosphoryl arabinose, the single donor of arabinosyl residues for the build-up of arabinans, fundamental components of the mycobacterial cell wall. This review presents the historical background leading to the discovery of DprE1, focusing on the biochemical and structural characterization of this important emerging target and introducing the molecules acting on DprE1 including the development of the most successful series – the benzothiazinones, currently in late pre-clinical development, which turned to be suicide inhibitors of DprE1.
Keywords: Tuberculosis, drug target, DprE1, structure, inhibitors, SAR, benzothiazinones.
Current Pharmaceutical Design
Title:DprE1 - from the Discovery to the Promising Tuberculosis Drug Target
Volume: 20 Issue: 27
Author(s): Katarina Mikusova, Vadim Makarov and Joao Neres
Affiliation:
Keywords: Tuberculosis, drug target, DprE1, structure, inhibitors, SAR, benzothiazinones.
Abstract: Several groups working in the field of the development of new antituberculosis drugs have recently reported active compounds targeting mycobacterial enzyme DprE1. Along with its counterpart, DprE2, it catalyses a unique epimerization reaction resulting in the synthesis of decaprenylphosphoryl arabinose, the single donor of arabinosyl residues for the build-up of arabinans, fundamental components of the mycobacterial cell wall. This review presents the historical background leading to the discovery of DprE1, focusing on the biochemical and structural characterization of this important emerging target and introducing the molecules acting on DprE1 including the development of the most successful series – the benzothiazinones, currently in late pre-clinical development, which turned to be suicide inhibitors of DprE1.
Export Options
About this article
Cite this article as:
Mikusova Katarina, Makarov Vadim and Neres Joao, DprE1 - from the Discovery to the Promising Tuberculosis Drug Target, Current Pharmaceutical Design 2014; 20 (27) . https://dx.doi.org/10.2174/138161282027140630122724
DOI https://dx.doi.org/10.2174/138161282027140630122724 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Preliminary Screening Indicates Promising Antimicrobial Properties of the Stem Bark Extracts of Macaranga rosea
Anti-Infective Agents Enzymatic Activity and Protein Interactions in Alpha/Beta Hydrolase Fold Proteins: Moonlighting Versus Promiscuity
Protein & Peptide Letters Interactions Between Proteins and Platinum-Containing Anti-Cancer Drugs
Mini-Reviews in Medicinal Chemistry Diagnosis and Therapeutic Approaches to Transthyretin Amyloidosis
Current Medicinal Chemistry Synthesis and Biological Evaluation of Arylthiourea Derivatives with Antitubercular Activity
Letters in Drug Design & Discovery Orchestration of Host-Pathogen Interaction: Relevance of Iron in Generation of Potent Anti-M. tuberculosis Immunity
Current Pharmaceutical Biotechnology 3D Modeling of Dengue Virus NS4B and Chikungunya Virus nsP4: Identification of a Common Drug Target and Designing a Single Antiviral Inhibitor
Current Computer-Aided Drug Design Metabolite Concentration as a Criterion for Antibacterial Discovery
Current Computer-Aided Drug Design Patent Selections
Recent Patents on Biotechnology Recent Patents on Self-Quenching DNA Probes
Recent Patents on DNA & Gene Sequences Subject Index To Volume 7
Current Pharmaceutical Design Organ Preference of Cancer Metastasis and Metastasis-Related Cell Adhesion Molecules Including Carbohydrates
Cardiovascular & Hematological Disorders-Drug Targets Metal-N-Heterocyclic Carbene Complexes as Anti-Tumor Agents
Current Medicinal Chemistry Patent Selections:
Recent Patents on Anti-Infective Drug Discovery Recent Updates on Applications of Lipid-Based Nanoparticles for Site- Specific Drug Delivery
Pharmaceutical Nanotechnology Potential Utility of Mycobacterium w Vaccine in Control of Tuberculosis
Current Respiratory Medicine Reviews Efficient Antibacterial Agents: A Review of the Synthesis, Biological Evaluation and Mechanism of Pleuromutilin Derivatives
Current Topics in Medicinal Chemistry Tackling Drug-Resistant Tuberculosis: Current Trends and Approaches
Mini-Reviews in Medicinal Chemistry A Structural-Energetic Basis for B-Cell Epitope Prediction
Protein & Peptide Letters DEFB1 5'UTR Polymorphisms Modulate the Risk of HIV-1 Infection in Mexican Women
Current HIV Research