Abstract
Plasmodium falciparum is one of the most lethal parasite responsible for human malaria. Until now, the only one solution to counter malaria is the use of antimalarial drugs. Unfortunately, the extensively use of drugs, such as quinolines (i.e. chloroquine, quinine or mefloquine), have led to the emergence of drug resistance. Chloroquine and probably other quinolines act in interfering in the detoxification of hematin in the digestive vacuole. Quinolines are accumulated in P. falciparum digestive vacuole and the accumulation varies from a susceptible strain to a resistant one. Nevertheless, the mechanisms of quinoline resistance are still investigating. Genetic polymorphisms in some strains have been linked to drug resistance. The modifications observed are mutations on genes that encode transport proteins localized in the membrane of digestive vacuole. Three transporters were involved in quinoline resistance: PfCRT (Plasmodium falciparum chloroquine resistance transporter), Pgh1 (P-glycoprotein homologue 1) and PfMRP (Plasmodium falciparum multidrug resistance protein). They could be involved in accumulation or efflux mechanisms of drugs. In order to understand their role in resistance, localization, encoding gene structure, protein structure and endogenous function of these three transporters are reported. Some molecules that have no intrinsic antimalarial effect have been shown to reverse drug resistance when they are combined to chloroquine, quinine or mefloquine. These molecules are a solution to counter resistance but also they are precious tools to elucidate the resistance mechanisms. The molecules that have already shown a capacity to reverse chloroquine, quinine or mefloquine resistances were reported. Some of them could act on one of the three transporters involved in drug resistance, by confirming their role in quinoline resistance. Here we summarize the main elements of quinoline resistance and reversion of quinoline resistance related to malaria.
Keywords: Antimalarial, drug resistance, quinoline, transporter, PfCRT, Pgh1, PfMRP, reversion
Current Topics in Medicinal Chemistry
Title: Inhibition of Efflux of Quinolines as New Therapeutic Strategy in Malaria
Volume: 8 Issue: 7
Author(s): Maud Henry, Sandrine Alibert, Christophe Rogier, Jacques Barbe and Bruno Pradines
Affiliation:
Keywords: Antimalarial, drug resistance, quinoline, transporter, PfCRT, Pgh1, PfMRP, reversion
Abstract: Plasmodium falciparum is one of the most lethal parasite responsible for human malaria. Until now, the only one solution to counter malaria is the use of antimalarial drugs. Unfortunately, the extensively use of drugs, such as quinolines (i.e. chloroquine, quinine or mefloquine), have led to the emergence of drug resistance. Chloroquine and probably other quinolines act in interfering in the detoxification of hematin in the digestive vacuole. Quinolines are accumulated in P. falciparum digestive vacuole and the accumulation varies from a susceptible strain to a resistant one. Nevertheless, the mechanisms of quinoline resistance are still investigating. Genetic polymorphisms in some strains have been linked to drug resistance. The modifications observed are mutations on genes that encode transport proteins localized in the membrane of digestive vacuole. Three transporters were involved in quinoline resistance: PfCRT (Plasmodium falciparum chloroquine resistance transporter), Pgh1 (P-glycoprotein homologue 1) and PfMRP (Plasmodium falciparum multidrug resistance protein). They could be involved in accumulation or efflux mechanisms of drugs. In order to understand their role in resistance, localization, encoding gene structure, protein structure and endogenous function of these three transporters are reported. Some molecules that have no intrinsic antimalarial effect have been shown to reverse drug resistance when they are combined to chloroquine, quinine or mefloquine. These molecules are a solution to counter resistance but also they are precious tools to elucidate the resistance mechanisms. The molecules that have already shown a capacity to reverse chloroquine, quinine or mefloquine resistances were reported. Some of them could act on one of the three transporters involved in drug resistance, by confirming their role in quinoline resistance. Here we summarize the main elements of quinoline resistance and reversion of quinoline resistance related to malaria.
Export Options
About this article
Cite this article as:
Henry Maud, Alibert Sandrine, Rogier Christophe, Barbe Jacques and Pradines Bruno, Inhibition of Efflux of Quinolines as New Therapeutic Strategy in Malaria, Current Topics in Medicinal Chemistry 2008; 8 (7) . https://dx.doi.org/10.2174/156802608783955593
DOI https://dx.doi.org/10.2174/156802608783955593 |
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
-
Gestational Exposure to Variable Stressors Produces Decrements in Cognitive and Neural Development of Juvenile Male and Female Rats
Current Topics in Medicinal Chemistry The Effects of Curcumin on Immune Responses
Current Bioactive Compounds Inhibition of Early Upstream Events in Prodromal Alzheimer’s Disease by Use of Targeted Antioxidants
Current Aging Science Alzheimer’s Disease Biomarkers and Epigenetic Intermediates Following Exposure to Pb In Vitro
Current Alzheimer Research Resveratrol Improves Cardiovascular Function in DOCA-Salt Hypertensive Rats
Current Pharmaceutical Biotechnology Conference Report: 10th Clinical Trials on Alzheimer's Disease (CTAD), Boston MA, USA, November 1-4, 2017
CNS & Neurological Disorders - Drug Targets Circadian Rhythm and Melatonin in the Treatment of Depression
Current Pharmaceutical Design Perylenebisimide-based Fluorescent Chemosensors for Selective Detection of Zn2+ in Aqueous Solution
Letters in Organic Chemistry Rediscovering Tocophersolan: A Renaissance for Nano-Based Drug Delivery and Nanotheranostic Applications
Current Drug Targets Freud Meets Bill W: A Model for the Dynamics of Alcoholics Anonymous
Adolescent Psychiatry Review: Involvement of the Cavum Septi Pellucidi and the Fornix in the Neuropathology of Schizophrenia and Affective Disorders
Current Psychiatry Reviews Alzheimer's Disease: Emerging Trends in Small Molecule Therapies
Current Medicinal Chemistry Cognitive Impairment Associated with Parkinson’s Disease: Role of Mitochondria
Current Neuropharmacology Interleukin-10: An Important Immunoregulatory Cytokine With Major Impact on Psoriasis
Current Drug Targets - Inflammation & Allergy Peripheral TRPV1 Receptors As Targets for Drug Development: New Molecules and Mechanisms
Current Pharmaceutical Design Possible Mechanisms of Action of NSAIDs and Related Compounds that Modulate γ - Secretase Cleavage
Current Topics in Medicinal Chemistry Computational Studies of Competitive Inhibitors of Nitric Oxide Synthase (NOS) Enzymes: Towards the Development of Powerful and Isoform-Selective Inhibitors
Current Medicinal Chemistry Dipeptidyl Peptidase IV Inhibitors: The Next Generation of New Promising Therapies for the Management of Type 2 Diabetes
Current Topics in Medicinal Chemistry A Closer Look to Polyesters: Properties, Synthesis, Characterization, and Particle Drug Delivery Applications
Nanoscience & Nanotechnology-Asia Viral Encephalitis: Current Treatments and Future Perspectives
Central Nervous System Agents in Medicinal Chemistry