A5037861926- Malaria Research and Control
- Mosquito-borne diseases and control
- Research on Leishmaniasis Studies
- Computational Drug Discovery Methods
- Trypanosoma species research and implications
- Eosinophilic Disorders and Syndromes
- Chronic Myeloid Leukemia Treatments
- HIV/AIDS drug development and treatment
- Pharmacological Effects of Natural Compounds
- Nigella sativa pharmacological applications
- HIV Research and Treatment
- Traditional and Medicinal Uses of Annonaceae
- RNA and protein synthesis mechanisms
- Insect Pest Control Strategies
- Coastal wetland ecosystem dynamics
- Bioactive Compounds and Antitumor Agents
- Fire effects on ecosystems
- Alkaloids: synthesis and pharmacology
- Moringa oleifera research and applications
- Phytochemical compounds biological activities
- Peatlands and Wetlands Ecology
- Invertebrate Immune Response Mechanisms
The University of Texas Southwestern Medical Center
2020-2023
Harvard University
2021-2023
Keele University
2013-2021
The mechanics of DNA replication and cell cycling are well-characterized in model organisms, but less is known about these basic aspects biology early-diverging Apicomplexan parasites, which do not divide by canonical binary fission undergo unconventional cycles. Schizogony the malaria parasite, Plasmodium, generates ~16-24 new nuclei via independent, asynchronous rounds genome prior to cytokinesis little control that facilitates this. We have characterised dynamics P. falciparum throughout...
The few frontline antileishmanial drugs are poorly effective and toxic. To search for new this neglected tropical disease, we tested the activity of compounds in Medicines Malaria Venture (MMV) "Pathogen Box" against Leishmania amazonensis axenic amastigotes. Screening yielded six discovery with EC50 values from 50 to 480 nM. Concentration–response assays demonstrated that best hit, MMV676477, had mid-nanomolar cytocidal potency intracellular amastigotes, Trypanosoma brucei, Plasmodium...
ABSTRACT Leishmania spp. are obligate intracellular parasites that must be internalized by phagocytic cells to evade immune responses and cause disease. The uptake of both promastigotes (insect-stage parasites) amastigotes (proliferative-stage in humans mice) phagocytes is thought mainly host cell driven, not parasite driven. Our previous work indicates Src- Abl-family kinases facilitate entry into macrophages pathogenesis murine cutaneous leishmaniasis. Here, we demonstrate spleen tyrosine...
A future treatment for uncomplicated malaria will contain at least one component that exerts a rapid rate of kill. We describe here the validation and application simple, robust bioluminescence-based assay determination initial kill in intra-erythrocytic asexual stages Plasmodium falciparum .A modification to concentration-response bioluminescence [here termed relative (BRRoK)] assay, utilizing exposure fold-IC 50 concentrations (0.33× 9×), was used monitor immediate cytocidal effect 372...
Rapid rate-of-kill (RoK) is a key parameter in the target candidate profile 1 (TCP1) for next-generation antimalarial drugs uncomplicated malaria, termed Single Encounter Radical Cure and Prophylaxis (SERCaP). TCP1 aims to rapidly eliminate initial parasite burden, ideally as fast artesunate, but minimally chloroquine. Here we explore whether relative RoK of Medicine Malaria Venture (MMV) Box compounds linked their mode action (MoA) identify scaffolds medicinal chemistry interest.We used...
Artemisinin (ART) combination therapies have been critical in reducing malaria morbidity and mortality, but these important drugs are threatened by growing resistance associated with mutations
Bisbenzylisoquinoline (BBIQ) alkaloids are a diverse group of natural products that demonstrate range biological activities. In this study, the in vitro antiplasmodial activity three BBIQ (cycleanine [compound 1], isochondodendrine 2], and 2′-norcocsuline 3]) isolated from Triclisia subcordata Oliv. medicinal plant traditionally used for treatment malaria Nigeria studied alongside two semisynthetic analogues (compounds 4 5) cycleanine.
The use of plant-derived natural products for the treatment tropical parasitic diseases often has ethnopharmacological origins. As such, plants grown in temperate regions remain largely untested novel anti-parasitic activities. We describe here a screen PhytoQuest Phytopure library, source comprising over 600 purified compounds from zone plants, against vitro culture systems Plasmodium falciparum, Leishmania mexicana, Trypanosoma evansi and T. brucei. Initial revealed 6, 65, 15 18 compounds,...
ABSTRACT Leishmania spp. are obligate intracellular parasites that must be internalized by phagocytic cells to evade immune responses and cause disease. The uptake of both promastigotes (insect-stage parasites) amastigotes (proliferative stage in humans mice) phagocytes is thought mainly host cell-driven, not parasite-driven. Our previous work indicates Src Abl family kinases facilitate entry into macrophages pathogenesis murine cutaneous leishmaniasis. Here we demonstrate spleen tyrosine...