A5003372044- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Synthesis and Biological Evaluation
- Parasites and Host Interactions
- Adenosine and Purinergic Signaling
- Calcium signaling and nucleotide metabolism
- Mosquito-borne diseases and control
- HIV/AIDS drug development and treatment
- Virology and Viral Diseases
- Medicinal Plants and Neuroprotection
- Malaria Research and Control
- Parasitic Diseases Research and Treatment
- Synthesis and Catalytic Reactions
- Biochemical and Molecular Research
- Macrophage Migration Inhibitory Factor
- Pneumocystis jirovecii pneumonia detection and treatment
- Quinazolinone synthesis and applications
- Alkaloids: synthesis and pharmacology
- bioluminescence and chemiluminescence research
- Venomous Animal Envenomation and Studies
University of Antwerp
2017-2025
Abstract African trypanosomiasis is a disease caused by Trypanosoma brucei parasites with limited treatment options. unable to synthesize purines de novo and relies solely on their uptake interconversion from the host, constituting purine nucleoside analogues potential source of antitrypanosomal agents. Here we combine structural elements known trypanocidal develop series 3’-deoxy-7-deazaadenosine nucleosides, investigate effects against trypanosomes. 3’-Deoxytubercidin highly potent...
Abstract Approximately 20% of sleeping sickness patients exhibit respiratory complications, however, with a largely unknown role the parasite. Here we show that tsetse fly-transmitted Trypanosoma brucei parasites rapidly and permanently colonize lungs occupy extravascular spaces surrounding blood vessels alveoli bronchi. They are present as nests multiplying exhibiting close interactions collagen active secretion extracellular vesicles. The local immune response shows substantial increase...
Three new chemical series (bicyclic nitroimidazoles, aminopyrazoles and oxaboroles) were selected by Drugs for Neglected Diseases initiative as potential drug leads leishmaniasis. Pharmacodynamics studies included both in vitro vivo efficacy, cross-resistance profiling against the current antileishmanial reference drugs evaluation of their cidal activity potential. Efficacy laboratory strains Leishmania infantum (MHOM/MA(BE)/67/ITMAP263) L. donovani (MHOM/ET/67/L82) was evaluated on...
Abstract Kinetoplastids are a group of flagellated protozoans including medically important parasites the genus Trypanosoma and Leishmania . The corresponding diseases have afflicted humans for centuries. In an effort to combat kinetoplastid infections, set 21 chalcones was synthesized evaluated their in vitro anti-protozoal efficacy against brucei , rhodesiense cruzi infantum To ensure safety, these compounds underwent selectivity evaluation by assessing toxicity human lung fibroblast cell...
Surra and Dourine are widespread diseases caused by two protozoan parasites Trypanosoma brucei evansi equiperdum, respectively. A wide range of animals including camels, horses, cattle buffaloes susceptible to infection. These pose a significant socio-economic burden, primarily due the limited therapeutic options complications associated with toxicity drug resistance, making disease management particularly challenging. This study evaluated potential 3'-deoxytubercidin, previously identified...
Since miltefosine monotherapy against visceral leishmaniasis (VL) caused by Leishmania donovani has been discontinued in the Indian subcontinent due to an increase number of treatment failures, single dose liposomal amphotericin B is now advocated as a option choice. Paromomycin-miltefosine combination therapy can be used substitute first-line regions without cold-chain potential. Previous laboratory studies closely related species infantum have demonstrated that paromomycin fairly rapidly...
Abstract In this study, Trypanosoma brucei was naturally transmitted to mice through the bites of infected Glossina morsitans tsetse flies. Neutrophils were recruited rapidly bite site, whereas monocytes attracted more gradually. Expression inflammatory cytokines ( il1b , il6 ), il10 and neutrophil chemokines cxcl1 cxcl5 ) transiently up-regulated at site parasite inoculation. Then, a second influx neutrophils occurred that coincided with previously described retention expansion in ear...
Animal trypanosomiasis (AT) is a parasitic disease with high socio-economic impact. Given the limited therapeutic options and problems of toxicity drug resistance, this study assessed redirecting our previously identified antitrypanosomal nucleosides for treatment AT. Promising hits were excellent in vitro activity across all important animal trypanosome species. Compound 7, an inosine analogue, described lead compound, 3'-deoxytubercidin (8), showed broad spectrum anti-AT activity,...
Human African trypanosomiasis is a neglected tropical disease caused by Trypanosoma brucei parasites. These protists are unable to produce the purine ring, making them vulnerable effects of nucleoside analogues. Starting from 3′-deoxytubercidin (5), lead compound with activity against central-nervous-stage human trypanosomiasis, we investigate structure–activity relationships and ribofuranose rings. The ring tolerated only modifications at C7, while many alterations 3′-deoxyribofuranosyl...
Trypanosomes and Leishmania are parasitic protozoans that affect millions of people globally. Herein we report the synthesis 2-aroyl quinazolinones their antiprotozoal efficacy against Trypanosoma brucei, brucei rhodesiense, cruzi, infantum. These compounds were counter-screened a human cell line for cytotoxicity. Thirteen twenty target in this study inhibited growth these parasites, with KJ1, KJ10 exhibiting IC50 values 4.7 μM (T. b. brucei) 1.1 rhodesiense), respectively.
Abstract Human African trypanosomiasis or sleeping sickness, caused by the protozoan parasite Trypanosoma brucei , is characterized manipulation of host’s immune response to ensure invasion and persistence. Uncovering key molecules that support establishment a prerequisite interfere with this process. We identified Q586B2 as T. protein induces IL-10 in myeloid cells, which promotes infection invasiveness. expressed during all life stages conserved Trypanosomatidae. Deleting Q586B2-encoding...
Current antileishmanial treatment is hampered by limitations, such as drug toxicity and the risk of failure, which may be related to parasitic resistance. Given urgent need for novel drugs, Drugs Neglected Diseases initiative (DNDi) has undertaken a discovery program, resulted in identification aminopyrazoles, highly promising chemical series. Multiple experiments have been performed anticipate propensity resistance development. Resistance selection was successive exposure Leishmania...
Human African trypanosomiasis is a neglected parasitic disease for which the current treatment options are quite limited. Trypanosomes not able to synthesize purines de novo and thus solely depend on purine salvage from host environment. This characteristic makes players of pathway putative drug targets. The activity known nucleoside analogues such as tubercidin cordycepin led development series C7-substituted analogues. Here, we use RNA interference (RNAi) libraries gain insight into...
Current treatment options for visceral leishmaniasis have several drawbacks, and clinicians are confronted with an increasing number of failures. To overcome this, the Drugs Neglected Diseases initiative (DNDi) has invested in development novel antileishmanial leads, including a very promising class oxaboroles. The mode action/resistance this series to Leishmania is still unknown may be important its further implementation. Repeated vivo drug exposure vitro selection procedure on both...
Type I interferons (IFNs) induced by an endogenous Leishmania RNA virus or exogenous viral infections have been shown to exacerbate with New World Cutaneous parasites, however, the impact of type IFNs in visceral and implicated mechanisms remain be unraveled. This study assessed IFN on macrophage infection L. infantum donovani implication sialoadhesin (Siglec-1/CD169, Sn) as IFN-inducible surface receptor. Stimulation bone marrow-derived macrophages (IFN-α) significantly enhanced...
The application of in vivo bioluminescent imaging infectious disease research has significantly increased over the past years. detection transgenic parasites expressing wildtype firefly luciferase is however hampered by a relatively low and heterogeneous tissue penetrating capacity emitted light. Solutions are sought using codon-optimized red-shifted luciferases that yield higher expression levels produce more red or near-infrared light, modified substrates with enhanced cell permeability...
Several members of the 3′,5′-cyclic nucleotide phosphodiesterase (PDE) family play an essential role in cellular processes, which has labeled them as interesting targets for various diseases. The parasitic protozoan Trypanosoma brucei , causative agent human African trypanosomiasis, contains several cyclic AMP specific PDEs from TbrPDEB1 is validated a drug target. recent discovery selective inhibitors increased their potential novel treatment this disease. Compounds characterized by rigid...
Abstract A series of novel pyrazolyl amide-chalcones conjugates was synthesized in five steps and evaluated against a range medically important kinetoplastid parasites including Trypanosoma cruzi , brucei rhodesiense Leishmania infantum . In addition, the also tested for vitro cytotoxicity activity human lung fibroblasts primary mouse macrophages. Among all synthetised compounds, 9b found to be most active T. b. with an IC 50 value 0.51 ± 0.06 μM. Against 9n potent 0.46 0.07 While L. 9a 7.16...
African trypanosomiasis is a widespread disease of human and veterinary importance caused by various