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Antiviral Research May 2020Recent publications have brought attention to the possible benefit of chloroquine, a broadly used antimalarial drug, in the treatment of patients infected by the novel... (Review)
Review
Recent publications have brought attention to the possible benefit of chloroquine, a broadly used antimalarial drug, in the treatment of patients infected by the novel emerged coronavirus (SARS-CoV-2). The scientific community should consider this information in light of previous experiments with chloroquine in the field of antiviral research.
Topics: Antiviral Agents; Betacoronavirus; COVID-19; China; Chloroquine; Clinical Trials as Topic; Coronavirus Infections; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; SARS-CoV-2
PubMed: 32147496
DOI: 10.1016/j.antiviral.2020.104762 -
Pharmacological Research Jun 2021Chloroquine (CQ) and hydroxychloroquine (HCQ) are the most common drugs used to relieve acute and chronic inflammatory diseases. In this article, we present a review... (Review)
Review
Chloroquine (CQ) and hydroxychloroquine (HCQ) are the most common drugs used to relieve acute and chronic inflammatory diseases. In this article, we present a review about the use of CQ and HCQ in antitumor therapies based on autophagy mechanisms. These molecules break/discontinue autophagosome-lysosome fusions in initial phases and enhance antiproliferative action of chemotherapeutics. Their sensitizing effects of chemotherapy when used as an adjuvant option in clinical trials against cancer. However, human related-MDR genes are also under risk to develop chemo or radioresistance because cancer cells have ability to throw 4-aminoquinolines out from digestive vacuoles well. Additionally, they also have antitumor mechanism unrelated to autophagy, including cell death from apoptosis and necroptosis and immunomodulatory/anti-inflammatory properties. However, the link between some anticancer mechanisms, clinical efficacy and pharmacological safety has not yet been fully defined.
Topics: Antineoplastic Agents; Autophagy; Chloroquine; Clinical Trials as Topic; Drug Resistance, Neoplasm; Humans; Hydroxychloroquine; Immunomodulating Agents; Neoplasms
PubMed: 33775862
DOI: 10.1016/j.phrs.2021.105582 -
Current Pharmaceutical Design 2020Chloroquine (CQ) and hydroxychloroquine (HCQ) are derivatives of the heterocyclic aromatic compound quinoline. These economical compounds have been used as antimalarial... (Review)
Review
Chloroquine (CQ) and hydroxychloroquine (HCQ) are derivatives of the heterocyclic aromatic compound quinoline. These economical compounds have been used as antimalarial agents for many years. Currently, they are used as monotherapy or in conjunction with other therapies for the treatment of autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren's syndrome (SS) and antiphospholipid antibody syndrome (APS). Based on its effects on the modulation of the autophagy process, various clinical studies suggest that CQ and HCQ could be used in combination with other chemotherapeutics for the treatment of various types of cancer. Furthermore, the antiviral effects showed against Zika, Chikungunya, and HIV are due to the annulation of endosomal/lysosomal acidification. Recently, CQ and HCQ were approved for the U.S. Food and Drug Administration (FDA) for the treatment of infected patients with the coronavirus SARSCoV- 2, causing the disease originated in December 2019, namely COVID-2019. Several mechanisms have been proposed to explain the pharmacological effects of these drugs: 1) disruption of lysosomal and endosomal pH, 2) inhibition of protein secretion/expression, 3) inhibition of antigen presentation, 4) decrease of proinflammatory cytokines, 5) inhibition of autophagy, 6) induction of apoptosis and 7) inhibition of ion channels activation. Thus, evidence has shown that these structures are leading molecules that can be modified or combined with other therapeutic agents. In this review, we will discuss the most recent findings in the mechanisms of action of CQ and HCQ in the immune system, and the use of these antimalarial drugs on diseases.
Topics: Autoimmune Diseases; Betacoronavirus; COVID-19; Chloroquine; Coronavirus Infections; Humans; Hydroxychloroquine; Immune System; Pandemics; Pneumonia, Viral; SARS-CoV-2
PubMed: 32634079
DOI: 10.2174/1381612826666200707132920 -
Recent Patents on Anti-cancer Drug... 2021Drug repurposing is emerging as an attractive strategy with lower attrition rate, lower cost and shorter timeframe than traditional drug discovery methods. Chloroquine... (Review)
Review
BACKGROUND
Drug repurposing is emerging as an attractive strategy with lower attrition rate, lower cost and shorter timeframe than traditional drug discovery methods. Chloroquine (CQ) and its analogs are old drugs originally indicated for malaria treatment. Serendipitous discovery in early years revealed its anti-inflammatory properties, thus allowing its repositioned use in autoimmune diseases. Recent evidence also suggested its potential therapeutic use for anticancer therapy.
OBJECTIVE
This article reviews the molecular mechanisms, clinical evaluation and recent patents of CQ analogs in cancer therapy.
METHODS
Literature and patent searches were conducted using PubMed database and Google Patent/ USPTO Patent Search database, respectively. The keywords including "chloroquine", "hydroxychloroquine", "chloroquine analogs", "chloroquine derivatives", "repurposing", "autophagy", and "cancer" were used.
RESULTS
CQ analogs have been reported to elicit their anticancer effects by modulating autophagy, inducing apoptosis, eliminating cancer stem cells, normalizing tumor vasculature and modulating antitumor immunity. As documented by recent patents and clinical trials, CQ analogs have been repurposed as an adjuvant therapy and combined with other anticancer agents for synergistic enhancement of treatment efficacy. However, most clinical trials on CQ only demonstrated modest improvement in anti-cancer efficacy.
CONCLUSION
Given that CQ loses its anticancer activity in acidic and hypoxic environment within a tumor, novel CQ analogs and/or their formulations are under active investigation to improve their physicochemical properties and biological activity. On the other hand, identification of new biomarkers for better patient selection has been advocated in future trials in order to realize the repurposing of CQ analogs for cancer treatment in a personalized manner.
Topics: Animals; Antineoplastic Agents; Apoptosis; Autophagy; Chemotherapy, Adjuvant; Chloroquine; Drug Repositioning; Humans; Hydroxychloroquine; Neoplasms; Patents as Topic
PubMed: 33413069
DOI: 10.2174/1574892815666210106111012 -
The American Journal of Emergency... Oct 2020Acute chloroquine and hydroxychloroquine toxicity is characterized by a combination of direct cardiovascular effects and electrolyte derangements with resultant... (Review)
Review
BACKGROUND
Acute chloroquine and hydroxychloroquine toxicity is characterized by a combination of direct cardiovascular effects and electrolyte derangements with resultant dysrhythmias and is associated with significant morbidity and mortality.
OBJECTIVE
This review describes acute chloroquine and hydroxychloroquine toxicity, outlines the complex pathophysiologic derangements, and addresses the emergency department (ED) management of this patient population.
DISCUSSION
Chloroquine and hydroxychloroquine are aminoquinoline derivatives widely used in the treatment of rheumatologic diseases including systemic lupus erythematosus and rheumatoid arthritis as well as for malaria prophylaxis. In early 2020, anecdotal reports and preliminary data suggested utility of hydroxychloroquine in attenuating viral loads and symptoms in patients with SARS-CoV-2 infection. Aminoquinoline drugs pose unique and significant toxicological risks, both during their intended use as well as in unsupervised settings by laypersons. The therapeutic range for chloroquine is narrow. Acute severe toxicity is associated with 10-30% mortality owing to a combination of direct cardiovascular effects and electrolyte derangements with resultant dysrhythmias. Treatment in the ED is focused on decontamination, stabilization of cardiac dysrhythmias, hemodynamic support, electrolyte correction, and seizure prevention.
CONCLUSIONS
An understanding of the pathophysiology of acute chloroquine and hydroxychloroquine toxicity and available emergency treatments can assist emergency clinicians in reducing the immediate morbidity and mortality associated with this disease.
Topics: Chloroquine; Drug Overdose; Emergency Service, Hospital; Humans; Hydroxychloroquine; Pandemics; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 33071096
DOI: 10.1016/j.ajem.2020.07.030 -
Applied Microbiology and Biotechnology Feb 2021The anti-malarial drugs chloroquine (CQ) and hydroxychloroquine (HCQ) have been suggested as promising agents against the new coronavirus SARS-CoV-2 that induces... (Review)
Review
The anti-malarial drugs chloroquine (CQ) and hydroxychloroquine (HCQ) have been suggested as promising agents against the new coronavirus SARS-CoV-2 that induces COVID-19 and as a possible therapy for shortening the duration of the viral disease. The antiviral effects of CQ and HCQ have been demonstrated in vitro due to their ability to block viruses like coronavirus SARS in cell culture. CQ and HCQ have been proposed to reduce immune reactions to infectious agents, inhibit pneumonia exacerbation, and improve lung imaging investigations. CQ analogs have also revealed the anti-inflammatory and immunomodulatory effects in treating viral infections and related ailments. There was, moreover, convincing evidence from early trials in China about the efficacy of CQ and HCQ in the anti-COVID-19 procedure. Since then, research and studies have been massive to ascertain these drugs' efficacy and safety in treating the viral disease. In the present review, we construct a synopsis of the main properties and current data concerning the metabolism of CQ/HCQ, which were the basis of assessing their potential therapeutic roles against the new coronavirus infection. The effective role of QC and HCQ in the prophylaxis and therapy of COVID-19 infection is discussed in light of the latest international medical-scientific research results. KEY POINTS: • Data concerning metabolism and properties of CQ/HCQ are discussed. • The efficacy of CQ/HCQ against COVID-19 has been the subject of contradictory results. • CQ/HCQ has little or no effect in reducing mortality in SARS-CoV-2-affected patients.
Topics: Antimalarials; Antiviral Agents; Chloroquine; Humans; Hydroxychloroquine; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 33515285
DOI: 10.1007/s00253-021-11094-4 -
Biochemical and Biophysical Research... Jan 2021At the end of last century a prominent biochemist once opened the discussion of a controversial issue in the field of Bioenergetics with the following statement: "This... (Review)
Review
At the end of last century a prominent biochemist once opened the discussion of a controversial issue in the field of Bioenergetics with the following statement: "This is a long story, that shouldn't be long, but it will take a long time to make it short". As it happens, such a statement would apply perfectly well to the story of chloroquine (CQ) and hydroxychloroquine (HCQ) in the COVID-19 infection: it has become a veritable saga, with conflicting views that have often gone beyond the normal scientific dialectic, and with conclusions that have frequently been polluted by non scientific opinions: thus, for instance, when National Agencies have taken positions against CQ and HCQ, the move has been seen as a pro-vaccine attempt to block low cost therapy means. And it is difficult to avoid the feeling that the opposition to CQ and HCQ has in large measure been shaped not by scientific arguments, but by the fact that their use has been strongly endorsed by National leaders whose popularity among Western intellectuals is extremely low. The role of the two drugs in the COVID-19 infection thus deserves an objective analysis solely based on scientific facts. This contribution will attempt to produce it.
Topics: COVID-19; Chloroquine; Humans; Hydroxychloroquine; Primary Prevention; COVID-19 Drug Treatment
PubMed: 33028485
DOI: 10.1016/j.bbrc.2020.09.128 -
Pharmacogenomics Oct 2023As substrates of CYP2C8, CYP3A4/5 and CYP2D6, chloroquine's (CQ) and hydroxychloroquine's (HCQ) efficacy and safety may be affected by variants in the genes encoding... (Review)
Review
As substrates of CYP2C8, CYP3A4/5 and CYP2D6, chloroquine's (CQ) and hydroxychloroquine's (HCQ) efficacy and safety may be affected by variants in the genes encoding these enzymes. This paper aims to assimilate the current evidence on the pharmacogenomics of CQ/HCQ and to identify risk phenotypes affecting the safety or efficacy of these drugs. It has been found that some , and genetic variants may affect the safety or effectiveness of CQ/HCQ. The phenotypes predictively representing ultra-rapid and poor metabolizers have been considered high-risk phenotypes. After considering these high-risk phenotypes in different ethnic groups, it is predicted that a considerable proportion of patients taking CQ/HCQ may be at risk of either therapeutic failure or severe toxicities.
Topics: Humans; Hydroxychloroquine; Chloroquine; Cytochrome P-450 CYP2C8; Cytochrome P-450 CYP2D6; Pharmacogenetics
PubMed: 37846548
DOI: 10.2217/pgs-2023-0124 -
Current Opinion in Immunology Oct 2020Due to the rapid onset and spread of the COVID-19 pandemic, the treatment of COVID-19 patients by hydroxychloroquine alone or in combination with other drugs has... (Review)
Review
Due to the rapid onset and spread of the COVID-19 pandemic, the treatment of COVID-19 patients by hydroxychloroquine alone or in combination with other drugs has captured a great deal of attention and triggered considerable debate. Historically, the worldwide use of quinoline based-drugs has led to a spectacular reduction in death from malaria. Unfortunately, scientists have been forced to seek alternative drugs to treat malaria due to the emergence of chloroquine-resistant parasites in the 1960s. The repurposing of hydroxychloroquine against viral infections, various types of cancer and autoimmune diseases has been ongoing for more than 70 years, with no clear understanding of its mechanism of action (MOA). Here, we closely examine the MOA of this old but influential drug in and beyond malaria. Better insights into how chloroquine targets the host's cellular and immune responses may help to develop applications against to new pathogens and diseases, and perhaps even restore the clinical utility of chloroquine against malaria.
Topics: Animals; Chloroquine; Humans; Hydroxychloroquine; Malaria; Pandemics; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 32823144
DOI: 10.1016/j.coi.2020.07.005 -
Human Toxicology Nov 1988High performance liquid chromatography was employed to quantify chloroquine in biological fluids and tissues in a death attributed to chloroquine overdose. The blood... (Review)
Review
High performance liquid chromatography was employed to quantify chloroquine in biological fluids and tissues in a death attributed to chloroquine overdose. The blood concentration of chloroquine was 16.71 mg/l. Results are discussed in the light of the existing literature.
Topics: Adult; Autopsy; Body Fluids; Chloroquine; Humans; Male; Suicide
PubMed: 3068119
DOI: 10.1177/096032718800700604