Abstract
Trypanosomatids consist of a large group of flagellated parasitic protozoa, including parasites from the genera Leishmania and Trypanosoma, responsible for causing infections in millions of humans worldwide and for which currently no appropriate therapy is available. The significance of pyrimidines in cellular metabolism makes their de novo and salvage pathways ideal druggable targets for pharmacological intervention and open an opportunity for pharmaceutical innovation. In the current review, we discuss the merits in targeting the enzyme dihydroorotate dehydrogenase (DHODH), a flavin-dependent enzyme that catalyzes the fourth and only redox step in pyrimidine de novo biosynthesis, as a strategy for the development of efficient therapeutic strategies for trypanosomatid-related diseases. We also describe the advances and perspectives from the structural biology point of view in order to unravel the structure-function relationship of trypanosomatid DHODHs, and to identify and validate target sites for drug development.
Keywords: Dihydroorotate dehydrogenase, trypanosomatids, Leishmania major, Trypanosoma cruzi, Trypanosoma brucei, sites for drug discovery
Current Pharmaceutical Design
Title:Target Sites for the Design of Anti-trypanosomatid Drugs Based on the Structure of Dihydroorotate Dehydrogenase
Volume: 19 Issue: 14
Author(s): Matheus Pinto Pinheiro, Flavio da Silva Emery and M. Cristina Nonato
Affiliation:
Keywords: Dihydroorotate dehydrogenase, trypanosomatids, Leishmania major, Trypanosoma cruzi, Trypanosoma brucei, sites for drug discovery
Abstract: Trypanosomatids consist of a large group of flagellated parasitic protozoa, including parasites from the genera Leishmania and Trypanosoma, responsible for causing infections in millions of humans worldwide and for which currently no appropriate therapy is available. The significance of pyrimidines in cellular metabolism makes their de novo and salvage pathways ideal druggable targets for pharmacological intervention and open an opportunity for pharmaceutical innovation. In the current review, we discuss the merits in targeting the enzyme dihydroorotate dehydrogenase (DHODH), a flavin-dependent enzyme that catalyzes the fourth and only redox step in pyrimidine de novo biosynthesis, as a strategy for the development of efficient therapeutic strategies for trypanosomatid-related diseases. We also describe the advances and perspectives from the structural biology point of view in order to unravel the structure-function relationship of trypanosomatid DHODHs, and to identify and validate target sites for drug development.
Export Options
About this article
Cite this article as:
Pinto Pinheiro Matheus, da Silva Emery Flavio and Cristina Nonato M., Target Sites for the Design of Anti-trypanosomatid Drugs Based on the Structure of Dihydroorotate Dehydrogenase, Current Pharmaceutical Design 2013; 19 (14) . https://dx.doi.org/10.2174/1381612811319140011
DOI https://dx.doi.org/10.2174/1381612811319140011 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
- 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
-
Targeting CSCs in Tumor Microenvironment: The Potential Role of ROS-Associated miRNAs in Tumor Aggressiveness
Current Stem Cell Research & Therapy The Immunological Function of iGb3
Current Protein & Peptide Science Atomistic Insights Into the Regulatory Mechanisms Mediated by Post- Translational Modifications: Molecular Dynamics Investigations
Current Physical Chemistry Short-Chain Fatty Acid Inhibitors of Histone Deacetylases: Promising Anticancer Therapeutics?
Current Cancer Drug Targets Structure, Functions and Selective Inhibitors of HDAC6
Current Topics in Medicinal Chemistry TRAIL-Based Therapeutic Approaches for the Treatment of Pediatric Malignancies
Current Medicinal Chemistry Nano-Sized Crystalline Drug Production by Milling Technology
Current Pharmaceutical Design Acute Renal Failure in Different Malignant Tumors
Current Medicinal Chemistry Lipid Nucleoside Conjugates for the Treatment of Cancer
Current Pharmaceutical Design Update on the Rheumatologic Manifestations of Malignancy
Current Cancer Therapy Reviews Natural Products as Exquisitely Potent Cytotoxic Payloads for Antibody- Drug Conjugates
Current Topics in Medicinal Chemistry TRAIL: A Sword for Killing Tumors
Current Medicinal Chemistry Dendritic Cell Immunotherapy for Malignant Gliomas
Reviews on Recent Clinical Trials MiRNAs in Human Cancers: The Diagnostic and Therapeutic Implications
Current Pharmaceutical Design Generation and Characterization of Monoclonal Antibodies Against Tth DNA Polymerase and its Application to Hot-Start PCR
Protein & Peptide Letters Azidothymidine is Effective Against Human Multiple Myeloma: A New Use for an Old Drug?
Anti-Cancer Agents in Medicinal Chemistry Novel Agents in the Management of Lung Cancer
Current Medicinal Chemistry MicroRNAs in Lymphoma: Regulatory Role and Biomarker Potential
Current Genomics Single-Photon Emission Computed Tomography Tracers for Predicting and Monitoring Cancer Therapy
Current Pharmaceutical Biotechnology Molecular Hybrids of N-Phthaloylglycyl Hydrazide and Hydrazinecarbothioamide with Anti-inflammatory and Anti-oxidant Activities
Current Organic Synthesis