Synthesis and biological evaluation of s-triazine substituted polyamines as potential new anti-trypanosomal drugs (Publications)
The P2 transporter is a nucleoside transporter which is unique to the protozoan parasite Trypanosoma brucei, the causative organism of Human African Trypanosomasis. The transporter has been shown to bind [...] substrate of the P2 transporter, as a potential tool to selectively deliver polyamine analogues to the parasites. The synthesis of a number of polyamine analogues attached to a variety of melamine analogues is [...] recognized by the transporter. Some of the compounds showed good in vitro...
Antiplasmodial activity of a series of 1,3,5-triazine-substituted polyamines (Publications)
has been shown to be a good drug target in some parasitic protozoa and it is proposed that the pathway might also represent a target in the malaria parasite Plasmodium falciparum. A series of 1,3,5-tria [...] tested for activity against Plasmodium falciparum in vitro. The series showed activity against the parasites and were generally more active against the chloroquine-resistant line K1 than the chloroquine-s
Synthesis and biological evaluation of s-triazine substituted polyamines as potential new anti-trypanosomal drugs (Publications)
The P2 transporter is a nucleoside transporter which is unique to the protozoan parasite Trypanosoma brucei, the causative organism of Human African Trypanosomasis. The transporter has been shown to bind [...] substrate of the P2 transporter, as a potential tool to selectively deliver polyamine analogues to the parasites. The synthesis of a number of polyamine analogues attached to a variety of melamine analogues is [...] recognized by the transporter. Some of the compounds showed good in vitro...
Antiplasmodial activity of a series of 1,3,5-triazine-substituted polyamines (Publications)
has been shown to be a good drug target in some parasitic protozoa and it is proposed that the pathway might also represent a target in the malaria parasite Plasmodium falciparum. A series of 1,3,5-tria [...] tested for activity against Plasmodium falciparum in vitro. The series showed activity against the parasites and were generally more active against the chloroquine-resistant line K1 than the chloroquine-s
Optimization of pyrazolopyridine 4-carboxamides with potent antimalarial activity for which resistance is associated with the <em>P. falciparum</em>... (Publications)
against parasites when the ABCI3 transporter was knocked down. The low metabolic stability intrinsic to the pyrazolopyridine scaffold and the slow rate by which the compounds kill asexual parasites resulted [...] antimalarial therapies. Toward this goal, high throughput screens against the P. falciparum asexual parasite identified the pyrazolopyridine 4-carboxamide scaffold. Structure-activity relationship analysis [...] while the inclusion of a 7'-aza-benzomorpholine on the 4-carboxamide motif...
A molecular marker of artemisinin-resistant <em>Plasmodium falciparum</em> malaria (Publications)
urgently needed. Here, using whole-genome sequencing of an artemisinin-resistant parasite line from Africa and clinical parasite isolates from Cambodia, we associate mutations in the PF3D7_1343700 kelch propeller [...] Cambodia. Strong correlations between the presence of a mutant allele, in vitro parasite survival rates and in vivo parasite clearance rates indicate that K13-propeller mutations are important determinants
A <em>Plasmodium falciparum</em> bromodomain protein regulates invasion gene expression (Publications)
falciparum, the parasite undergoes repeated rounds of replication, egress, and invasion. Erythrocyte invasion involves specific interactions between host cell receptors and parasite ligands and coordinated [...] coordinated expression of genes specific to this step of the life cycle. We show that a parasite-specific bromodomain protein, PfBDP1, binds to chromatin at transcriptional start sites of invasion-related genes [...] and directly controls their expression. Conditional PfBDP1 knockdown...
Genesis of and trafficking to the Maurer's clefts of <em>Plasmodium falciparum</em>-infected erythrocytes (Publications)
Malaria parasites export proteins beyond their own plasma membrane to locations in the red blood cells in which they reside. Maurer's clefts are parasite-derived structures within the host cell cytoplasm [...] cytoplasm that are thought to function as a sorting compartment between the parasite and the erythrocyte membrane. However, the genesis of this compartment and the signals directing proteins to the Maurer's [...] domain are successfully delivered to Maurer's clefts. Other fragments...
Multiplexed ddPCR-amplicon sequencing reveals isolated <em>Plasmodium falciparum</em> populations amenable to local elimination in Zanzibar, Tanzania (Publications)
pronounced fine-scale spatial and temporal parasite genetic structure. Clusters of near-clonal infections on Pemba indicate persistent local transmission with limited parasite importation, presenting an opportunity [...] opportunity for local elimination efforts. Furthermore, we observe an admixed parasite population on Unguja and detect a substantial fraction (2.9%) of significantly related infection pairs between Zanzibar [...] Zanzibar and the mainland, suggesting recent importation. Our...
Major surface glycoproteins of insect forms of <em>Trypanosoma brucei</em> are not essential for cyclical transmission by tsetse (Publications)
ylinositol-anchored proteins known as procyclins. It has been proposed that procyclins protect parasites against proteases and/or participate in tropism, directing them from the midgut to the salivary [...] procyclins are essential for survival and transmission of T. brucei, all four genes were deleted and parasite fitness was compared in vitro and in vivo. When co-cultured in vitro, the null mutant and wild type [...] in vivo. Although the null mutant is patently defective in competition with...
