Abstract
Since the recent renaissance of phenotypic screening in the field of protozoan drug discovery, is there still an opportunity for the structure-based design of new anti-protozoan agents? Target-based approaches should be used in parallel to phenotypic screening to strengthen the pipeline of anti-protozoan agents. We give an overview of the protozoan drug discovery landscape highlighting four protein targets of interest: cytochrome bc1, dihydroorotate dehydrogenase, dihydrofolate reductase and calcium-dependent protein kinase 1. We discuss recent structurebased design efforts to inhibit these targets, reviewing their crystal structures and their ability to accommodate potent and selective compounds. Finally, we discuss future opportunities to apply structure-based methods to promising molecular targets within protozoan parasites discovered using chemical genomics.
Keywords: Apicomplexan drug discovery, CDPK1, Cytochrome bc1, DHFR, DHODH, Structure-based design.
Current Topics in Medicinal Chemistry
Title:New Opportunities in the Structure-based Design of Anti-Protozoan Agents
Volume: 17 Issue: 1
Author(s): James A. Gordon, Colin W.G. Fishwick and Martin J. McPhillie
Affiliation:
Keywords: Apicomplexan drug discovery, CDPK1, Cytochrome bc1, DHFR, DHODH, Structure-based design.
Abstract: Since the recent renaissance of phenotypic screening in the field of protozoan drug discovery, is there still an opportunity for the structure-based design of new anti-protozoan agents? Target-based approaches should be used in parallel to phenotypic screening to strengthen the pipeline of anti-protozoan agents. We give an overview of the protozoan drug discovery landscape highlighting four protein targets of interest: cytochrome bc1, dihydroorotate dehydrogenase, dihydrofolate reductase and calcium-dependent protein kinase 1. We discuss recent structurebased design efforts to inhibit these targets, reviewing their crystal structures and their ability to accommodate potent and selective compounds. Finally, we discuss future opportunities to apply structure-based methods to promising molecular targets within protozoan parasites discovered using chemical genomics.
Export Options
About this article
Cite this article as:
Gordon A. James, Fishwick W.G. Colin and McPhillie J. Martin, New Opportunities in the Structure-based Design of Anti-Protozoan Agents, Current Topics in Medicinal Chemistry 2017; 17 (1) . https://dx.doi.org/10.2174/1568026616666160719164542
DOI https://dx.doi.org/10.2174/1568026616666160719164542 |
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
-
Role of CD14 in Host Response to Infection
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Delivery of Anti-Viral Nucleoside Analogues to the Central Nervous System
Current Medicinal Chemistry - Anti-Infective Agents ABC Transporters in the CNS – An Inventory
Current Pharmaceutical Biotechnology Updating the Chemistry and Biology of Cannabinoid CB2 Receptor – Specific Inverse Agonists
Current Topics in Medicinal Chemistry Neurocysticercosis: The Enigmatic Disease
Central Nervous System Agents in Medicinal Chemistry Large-Scale Production Means for the Manufacturing of Lentiviral Vectors
Current Gene Therapy Analysis of TLC-Bioautography and TLC-Spot Visualization of <i>Atropa accuminata</i> and <i>Atropa belladonna</i> Extracts as Antioxidant and Antibacterial Agents Against Human Pathogenic Bacteria
Current Pharmaceutical Analysis The Potential Role of Pro-Inflammatory and Anti-Inflammatory Cytokines in Epilepsy Pathogenesis
Endocrine, Metabolic & Immune Disorders - Drug Targets Biological Drugs in Guillain-Barré Syndrome: An Update
Current Neuropharmacology Par-4 for Molecular Therapy of Prostate Cancer
Current Drug Targets Pharmaceutical Targeting of the Brain
Current Pharmaceutical Design CCL2-CCR2 Signaling in Disease Pathogenesis
Endocrine, Metabolic & Immune Disorders - Drug Targets Peripheral Benzodiazepine Receptor Ligands and their Anti-Inflammatory Effects
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents DNA Microarrays - An Armory for Combating Infectious Diseases in the New Century
Infectious Disorders - Drug Targets Novel Phospholipase-Resistant Lipid/Peptide Synthetic Lung Surfactants
Mini-Reviews in Medicinal Chemistry CNS Immune Surveillance and Neuroinflammation: Endocannabinoids Keep Control
Current Pharmaceutical Design Evaluation of B Lymphocyte Deficiencies
Cardiovascular & Hematological Disorders-Drug Targets Abeta Immunotherapy and Other Means to Remove Amyloid
Current Drug Targets - CNS & Neurological Disorders Synthesis and Biological Evaluation of a Series of 4-(arylamido/imidoalkyl)- 5-(arylideno- 4-oxo-2-thio-imidazolidinyl)-N-(methyl-phenyl-imino) Acridinium Iodides as Potential Antiviral Agents
Letters in Drug Design & Discovery The CCL2/CCR2 Axis in the Pathogenesis of HIV-1 Infection: A New Cellular Target for Therapy?
Current Drug Targets