Search results for "MALARIA"
showing 10 items of 169 documents
Social interactions modulate the virulence of avian malaria infection
2013
There is an increasing understanding of the context-dependent nature of parasite virulence. Variation in parasite virulence can occur when infected individuals compete with conspecifics that vary in infection status; virulence may be higher when competing with uninfected competitors. In vertebrates with social hierarchies, we propose that these competition-mediated costs of infection may also vary with social status. Dominant individuals have greater competitive ability than competing subordinates, and consequently may pay a lower prevalence-mediated cost of infection. In this study we investigated whether costs of malarial infection were affected by the occurrence of the parasite in compet…
Prevention of carcinogenesis and metastasis by Artemisinin-type drugs.
2018
Artemisia annua (sweet wormwood, qinhao) is an ancient Chinese herbal remedy for pyrexia. Nowadays, artemisinin (qinghaosu) and its derivatives belong to the standard therapies against malaria worldwide, and its discovery has led to the Nobel Prize in Physiology and Medicine to Youyou Tu in 2015. While most attention has been paid to the treatment of malaria, there is increasing evidence that Artemisinin-type drugs bear a considerable potential to treat and prevent cancer. Rather than reporting on therapy of cancer, this review gives a comprehensive and timely overview on the chemopreventive effects of artemisinin and its derivatives against carcinogenesis and metastasis formation, followin…
Repurposing of artemisinin-type drugs for the treatment of acute leukemia.
2020
Cancer treatment represents an unmet challenge due to the development of drug resistance and severe side effects of chemotherapy. Artemisinin (ARS)-type compounds exhibit excellent antimalarial effects with few side effects and drug-resistance. ARS and its derivatives were also reported to act against various tumor types in vitro and in vivo, including acute leukemia. Therefore, ARS-type compounds may be exquisitely suitable for repurposing in leukemia treatment. To provide comprehensive clues of ARS and its derivatives for acute leukemia treatment, their molecular mechanisms are discussed in this review. Five monomeric molecules and 72 dimers, trimers and hybrids based on the ARS scaffold …
Development of Novel Peptide-Based Michael Acceptors Targeting Rhodesain and Falcipain-2 for the Treatment of Neglected Tropical Diseases (NTDs)
2017
This paper describes the development of a class of peptide-based inhibitors as novel antitrypanosomal and antimalarial agents. The inhibitors are based on a characteristic peptide sequence for the inhibition of the cysteine proteases rhodesain of Trypanosoma brucei rhodesiense and falcipain-2 of Plasmodium falciparum. We exploited the reactivity of novel unsaturated electrophilic functions such as vinyl-sulfones, -ketones, -esters, and -nitriles. The Michael acceptors inhibited both rhodesain and falcipain-2, at nanomolar and micromolar levels, respectively. In particular, the vinyl ketone 3b has emerged as a potent rhodesain inhibitor (k2nd = 67 × 106 M-1 min-1), endowed with a picomolar b…
Biosynthesis of heme O in intraerythrocytic stages of Plasmodium falciparum and potential inhibitors of this pathway
2019
A number of antimalarial drugs interfere with the electron transport chain and heme-related reactions; however, the biosynthesis of heme derivatives in Plasmodium parasites has not been fully elucidated. Here, we characterized the steps that lead to the farnesylation of heme. After the identification of a gene encoding heme O synthase, we identified heme O synthesis in blood stage parasites through the incorporation of radioactive precursors. The presence of heme O synthesis in intraerythrocytic stages of Plasmodium falciparum was confirmed by mass spectrometry. Inabenfide and uniconazole–P appeared to interfere in heme synthesis, accordingly, parasite growth was also affected by the additi…
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…
Vitamin D in malaria: more hypotheses than clues
2019
Abstract Vitamin D is a secosteroid hormone regulating calcium and phosphate metabolism, immune response and brain development. Low blood 25(OH)D levels have been reported in patients affected by infectious diseases caused by parasites, including malaria. Despite the high effectiveness of antimalarials, malaria is burdened with high morbidity and mortality, and the search for additional therapies is rapidly growing. Furthermore, available preventive measures have proved to be barely effective so far. Finding new prevention and therapy tools is a matter of urgency. Studies on animal models and humans have hypothesized some mechanisms by which the hormone can influence malaria pathogenesis, a…
Age reduces resistance and tolerance in malaria-infected mice.
2021
7 pages; International audience; Once infected, hosts can rely on two strategies to cope with parasites: fight them (resist the infection) or minimize the damage they induce (tolerate the infection). While there is evidence that aging reduces resistance, how tolerance varies as hosts become old has been barely studied. Here, we used a rodent malaria parasite (Plasmodium yoelii) to investigate whether 2- and 12-month old house mice differ in their capacity to resist and tolerate the infection. We found that 12-month old mice harbored higher parasitemia, showing that age reduces resistance to malaria. Infection-induced deterioration of host health was assessed using red blood cell and body ma…
Evaluation of Mucociliary Clearance by Three Dimension Micro-CT-SPECT in Guinea Pig: Role of Bitter Taste Agonists
2016
Different image techniques have been used to analyze mucociliary clearance (MCC) in humans, but current small animal MCC analysis using in vivo imaging has not been well defined. Bitter taste receptor (T2R) agonists increase ciliary beat frequency (CBF) and cause bronchodilation but their effects in vivo are not well understood. This work analyzes in vivo nasal and bronchial MCC in guinea pig animals using three dimension (3D) microCT-SPECT images and evaluates the effect of T2R agonists. Intranasal macroaggreggates of albumin-Technetium 99 metastable (MAA-Tc99m) and lung nebulized Tc99m albumin nanocolloids were used to analyze the effect of T2R agonists on nasal and bronchial MCC respecti…
Synthesis of Thymoquinone–Artemisinin Hybrids: New Potent Antileukemia, Antiviral, and Antimalarial Agents
2017
[Image: see text] A series of hybrid compounds based on the natural products artemisinin and thymoquinone was synthesized and investigated for their biological activity against the malaria parasite Plasmodium falciparum 3D7 strain, human cytomegalovirus (HCMV), and two leukemia cell lines (drug-sensitive CCRF-CEM and multidrug-resistant subline CEM/ADR5000). An unprecedented one-pot method of selective formation of C-10α-acetate 14 starting from a 1:1 mixture of C-10α- to C-10β-dihydroartemisinin was developed. The key step of this facile method is a mild decarboxylative activation of malonic acid mediated by DCC/DMAP. Ether-linked thymoquinone–artemisinin hybrids 6a/b stood out as the most…