Search results for "chloroquine"

Synthesis of 3-azabicyclo[3.2.2]nonanes and their antiprotozoal activities.

2015

Several bicyclic compounds, 3-azabicyclo[3.2.2]nonanes, have been prepared. The new compounds were tested for their activities against one strain of the causative organism of Malaria tropica, Plasmodium falciparum K1, which is resistant against chloroquine and pyrimethamine. In addition, their cytotoxicity and their activity against the pathogen of the East African form of sleeping sickness, Trypanosoma brucei rhodesiense, were investigated. Structure-activity relationships are discussed considering data of readily prepared compounds. For the first time, a distinct in vivo activity was observed against Plasmodium berghei in a mouse model. The active compound was further investigated.

Clinical characteristics of patients hospitalized with COVID-19 in Spain: results from the SEMI-COVID-19 Network

2020

ABSTRACTBackgroundSpain has been one of the countries most affected by the COVID-19 pandemic.ObjectiveTo create a registry of patients with COVID-19 hospitalized in Spain in order to improve our knowledge of the clinical, diagnostic, therapeutic, and prognostic aspects of this disease.MethodsA multicentre retrospective cohort study, including consecutive patients hospitalized with confirmed COVID-19 throughout Spain. Epidemiological and clinical data, additional tests at admission and at seven days, treatments administered, and progress at 30 days of hospitalization were collected from electronic medical records.ResultsUp to April 30th 2020, 6,424 patients from 109 hospitals were included. …

Inhibition of autophagy rescues muscle atrophy in a LGMDD2 Drosophila model

2021

Limb-girdle muscular dystrophy D2 (LGMDD2) is an ultrarare autosomal dominant myopathy caused by mutation of the normal stop codon of the TNPO3 nuclear importin. The mutant protein carries a 15 amino acid C-terminal extension associated with pathogenicity. Here we report the first animal model of the disease by expressing the human mutant TNPO3 gene in Drosophila musculature or motor neurons and concomitantly silencing the endogenous expression of the fly protein ortholog. A similar genotype expressing wildtype TNPO3 served as a control. Phenotypes characterization revealed that mutant TNPO3 expression targeted at muscles or motor neurons caused LGMDD2-like phenotypes such as muscle degener…

Hyperpigmentation of hard palate induced by chloroquine therapy

2017

The antimalarials are one of the most commonly prescribed drugs for conditions such as lupus erythematosus and rheumatoid arthritis, and the side effects, though infrequent, are well known. The antimalarial agent chloroquine diphosphate usually causes pigmentary changes in the oral mucosa characterized by a bluish-grey to black discolorations mainly in the hard palate. Considering only the hard palate hyperpigmentation caused by chloroquine, to the best of our knowledge, only 13 cases have been reported in the English language literature. We described an additional case of palate hyperpigmentation related to the chronic use of chloroquine diphosphate in a 60-year-old Mexican woman. Although…

Access to new highly potent antileukemia, antiviral and antimalarial agents via hybridization of natural products (homo)egonol, thymoquinone and arte…

2018

Hybridization of natural products has high potential to further improve their activities and may produce synergistic effects between linked pharmacophores. Here we report synthesis of nine new hybrids of natural products egonol, homoegonol, thymoquinone and artemisinin and evaluation of their activities against P. falciparum 3D7 parasites, human cytomegalovirus, sensitive and multidrug-resistant human leukemia cells. Most of the new hybrids exceed their parent compounds in antimalarial, antiviral and antileukemia activities and in some cases show higher in vitro efficacy than clinically used reference drugs chloroquine, ganciclovir and doxorubicin. Combined, our findings stress the high pot…

Discovery of new antimalarial compounds by use of molecular connectivity techniques.

1999

Abstract Molecular connectivity has been applied to the search for new compounds with antimalarial activity. Linear discriminant analysis and connectivity functions were used to select several potentially suitable drugs which were tested for antimalarial properties by use of an in-vitro micro test which estimates parasite growth by measurement of incorporation of [3H]hypoxanthine. Hexetidine stands out among the compounds selected. Activity assays were performed with Plasmodium falciparum passou and 3CD7 strains, for which the IC50 values (doses resulting in 50% inhibition) were 320 and 400 ng mL−1 respectively. These results are comparable with those obtained for quinine chlorhydrate (IC50…

Functional characterization of ORCTL2--an organic cation transporter expressed in the renal proximal tubules.

1998

AbstractChromosome 11p15.5 harbors a gene or genes involved in Beckwith-Wiedemann syndrome that confer(s) susceptibility to Wilms' tumor, rhabdomyosarcoma, and hepatoblastoma. We have previously identified a transcript at 11p15.5 which encodes a putative membrane transport protein, designated organic cation transporter-like 2 (ORCTL2), that shares homology with tetracycline resistance proteins and bacterial multidrug resistance proteins. In this report, we have investigated the transport properties of ORCTL2 and show that this protein can confer resistance to chloroquine and quinidine when overexpressed in bacteria. Immunohistochemistry analyses performed with anti-ORCTL2 polyc.onal antibod…

2017

Many quinazoline derivatives have been synthesized over the last few decades with great pharmacological potential, such as antimalarial, anti-inflammatory, antimicrobial, anticancer, and antiviral. But so far, no quinazoline–artemisinin hybrids have been reported in the literature. In the present study, five novel quinazoline–artemisinin hybrids were synthesized and evaluated for their in vitro biological activity against malarial parasites (Plasmodium falciparum 3D7), leukemia cells (CCRF-CEM and CEM/ADR5000), and human cytomegalovirus. Remarkably, hybrid 9 (EC50 = 1.4 nM), the most active antimalarial compound of this study, was not only more potent than artesunic acid (EC50 = 9.7 nM) but…

Decreased Perifoveal Sensitivity Detected by Microperimetry in Patients Using Hydroxychloroquine and without Visual Field and Fundoscopic Anomalies

2015

Purpose. To evaluate the usefulness of microperimetry in the early detection of the ocular anomalies associated with the use of hydroxychloroquine.Methods. Prospective comparative case series study comprising 14 healthy eyes of 7 patients (group A) and 14 eyes of 7 patients under treatment with hydroxychloroquine for the treatment of rheumatologic diseases and without fundoscopic or perimetric anomalies (group B). A comprehensive ophthalmological examination including microperimetry (MP) and spectral-domain optical coherence tomography was performed in both groups.Results. No significant differences were found in mean MP foveal sensitivity between groupsP=0.18. However, mean MP overall sens…

An umbrella review of systematic reviews with meta-analyses evaluating positive and negative outcomes of Hydroxychloroquine and chloroquine therapy

2021

Background & aims: Hydroxychloroquine (HCQ) and chloroquine (CQ) are anti-malarial drugs frequently used in the rheumatologic field. They were recently identified as potential therapeutic options for Coronavirus Disease (COVID-19). The present study aims to map and grade the diverse health outcomes associated with HCQ/CQ using an umbrella review approach. Methods: Umbrella review of systematic reviews of observational and intervention studies. For observational studies, random-effects summary effect size, 95% confidence interval, and 95% prediction interval were estimated. We also assessed heterogeneity, evidence for small-study effect, and evidence for excess significance bias. The quality…