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Melatonin acts to synchronize the parasite's intraerythrocytic cycle by triggering the phospholipase -inositol 1,4,5-trisphosphate (PLC-IP) signaling cascade. Compounds with an indole scaffold impair in vitro proliferation of blood-stage malaria parasites, indicating that this class of compounds is potentially emerging antiplasmodial drugs. Therefore, we aimed to study the role of the alkyl and aryl thiol moieties of 14 synthetic indole compounds against chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) strains of . Four compounds (, , , ) inhibited the growth of (3D7) by 50% at concentrations below 20 µM. A set of 2-sulfenylindoles also showed activity against Dd2 parasites. Our data suggest that Dd2 parasites are more susceptible to compounds and than 3D7 parasites. These data show that 2-sulfenylindoles are promising antimalarials against chloroquine-resistant parasite strains. We also evaluated the effects of the 14 compounds on the parasitemia of the 3D7 strain and their ability to interfere with the effect of 100 nM melatonin on the parasitemia of the 3D7 strain. Our results showed that compounds , , , , , , , and slightly increased the effect of melatonin by increasing parasitemia by 8-20% compared with that of melatonin-only-treated 3D7 parasites. Moreover, we found that melatonin modulates the expression of kinase-related signaling components giving additional evidence to investigate inhibitors that can block melatonin signaling.
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http://dx.doi.org/10.3390/biom12050638 | DOI Listing |
Malar J
December 2024
Laboratoire d'Entomologie, UFR Sciences de la Nature, Université Nangui Abrogoua, Abidjan, Côte d'Ivoire.
Background: Malaria remains a threat in sub-Saharan Africa, particularly in Côte d'Ivoire, where it is endemic and represents the leading cause of hospital consultations, morbidity and mortality. The strong climatic variations that exist between coastal and savannah areas of Côte d'Ivoire suggest that vector control interventions should be scheduled according to the eco-epidemiological diversity. This study evaluates bioecological parameters of vectors and malaria transmission in two health districts, one coastal and one central of Côte d'Ivoire.
View Article and Find Full Text PDFAm J Trop Med Hyg
December 2024
Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China.
Although China has achieved malaria elimination certification, the risk of malaria transmission reintroduction due to imported malaria remains. We analyzed data on imported malaria cases collected from January 1, 2014 to December 31, 2021, using multivariable logistic regression analysis to identify the factors associated with severe and relapsing malaria. The odds of severe malaria were around 4-fold greater for patients who were initially diagnosed with a nonmalarial illness than for patients initially diagnosed with malaria.
View Article and Find Full Text PDFJ Math Biol
December 2024
School of Mathematics and Statistics, The University of Melbourne, Parkville, Australia.
The epidemiological behavior of Plasmodium vivax malaria occurs across spatial scales including within-host, population, and metapopulation levels. On the within-host scale, P. vivax sporozoites inoculated in a host may form latent hypnozoites, the activation of which drives secondary infections and accounts for a large proportion of P.
View Article and Find Full Text PDFLancet Infect Dis
December 2024
Training and Research Unit of Excellence, Blantyre, Malawi; School of Global and Public Health, Kamuzu University of Health Sciences, Blantyre, Malawi.
Background: In many sub-Saharan African countries, it is recommended that children with sickle cell anaemia receive malaria chemoprevention with monthly sulfadoxine-pyrimethamine or daily proguanil as the standard of care. However, the efficacy of these interventions is compromised by high-grade antifolate resistance of Plasmodium falciparum and poor adherence. We aimed to compare the efficacy of weekly dihydroartemisinin-piperaquine and monthly sulfadoxine-pyrimethamine for the prevention of clinical malaria in children with sickle cell anaemia in areas with high-grade sulfadoxine-pyrimethamine resistance of P falciparum in Uganda and Malawi.
View Article and Find Full Text PDFFront Immunol
December 2024
Division of Infectious Diseases, Department of Medicine Solna and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Introduction: Malaria remains a significant burden, and a fully protective vaccine against is critical for reducing morbidity and mortality. Antibody responses against the blood-stage antigen Merozoite Surface Protein 2 (MSP2) are associated with protection from malaria, but its extensive polymorphism is a barrier to its development as a vaccine candidate. New tools, such as long-read sequencing and accurate protein structure modelling allow us to study the genetic diversity and immune responses towards antigens from clinical isolates with unprecedented detail.
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