Chemical decomposition of DMSO stock solutions is a common incident that can mislead biological screening campaigns. Here, we share our case study of 2-aminothiazole 1, originating from an antimalarial class that undergoes chemical decomposition in DMSO at room temperature. As previously measured biological activities observed against Plasmodium falciparum NF54 and for the target enzyme Pf IspE were not reproducible for a fresh batch, we tackled the challenge to understand where the activity originated from.
P218 is a highly selective dihydrofolate reductase inhibitor with potent in vitro activity against pyrimethamine-resistant Plasmodium falciparum. This single-center, randomized, double-blind, placebo-controlled phase Ib study evaluated P218 safety and chemoprotective efficacy in a P. falciparum sporozoite (PfSPZ) volunteer infection study (VIS). Consecutive dose safety and tolerability were evaluated (cohort 1), with participants receiving two oral doses of P218 1,000 mg 48 hours apart (n = 6), or placebo (n = 2). P218 chemoprotective efficacy was assessed (cohorts 2 and 3) with direct venous inoculation of 3,200 aseptic, cryopreserved PfSPZ (NF54 strain) followed 2 hours later with two P218 doses of 1,000 mg (cohort 2, n = 9) or 100 mg (cohort 3, n = 9) administered 48 hours apart, or placebo (n = 6).
A total synthesis of dehydroantofine was achieved by employing a novel, regioselective azahetero Diels-Alder reaction of the easily accessible 3,5-dichloro-2 H -1,4-oxazin-2-one with 4-ethynyl-1,2-dimethoxybenzene as a key step.
Malaria is caused by different species of Plasmodium; among which P. falciparum is the most severe. Coptis teeta is an ethnomedicinal plant of enormous importance for tribes of north east India.
Variable and low oral bioavailability (4-11%) of lumefantrine (LUF), an anti-malarial agent, is characterized by very low solubility in aqueous vehicle. Thus, the present study was intended to formulate lyophilized nanosuspensions of LUF to resolve its solubility issues for the improvement of oral bioavailability. A three level 32 factorial design was applied to analyze the influence of independent variables, concentration of polysorbate 80 (X1) and sonication time (X2) on the responses for dependent variables, particle size (Y1) and time to 90% release of LUF (t90) (Y2).
Malaria continues to become a major global health problem, particularly in Sub-Saharan Africa, Asia, and Latin America. The widespread emergence of resistance to first-line drugs has further bolstered an urgent need for a new and cost-effective antimalarial(s). Thus, the present study enumerates the synthesis of novel hybrid dimethoxy pyrazole 1,3,5-triazine derivatives 7(a-j) and their in silico results short-listed three compounds with good binding energies and dock scores.
The aim of the current research to formulate a nano delivery system for effective delivery of primaquine for liver targeting to achieve the potential antimalarial activity. An objective of current development is to formulate a lactobionic acid conjugated polyphosphazene based nanodelivery of primaquine for liver targeting to distinguish antimalarial activity.
In areas of high transmission, malaria in pregnancy (MiP) primarily causes asymptomatic infections; these infections nonetheless increase the risk of adverse maternal and fetal outcomes. In 2014, Tanzania initiated a single screening and treatment (SST) strategy for all pregnant women at their first antenatal care (ANC) visit using malaria rapid diagnostic tests (RDT) for surveillance purposes. However, there is paucity of data on the effectiveness of SST in the prevention of MiP. The objective of this study was to estimate the number of asymptomatic infections among pregnant women detected by SST, which would have been missed in the absence of the policy.
A series of tetrahydro-β-carboline derivatives of a lead compound known to target the heat shock 90 protein of Plasmodium falciparum were synthesized and assayed for both potency against the parasite and toxicity against a human cell line.
Doxycycline (DOX) is a key antimalarial drug thought to kill Plasmodium parasites by blocking protein translation in the essential apicoplast organelle. Clinical use is primarily limited to prophylaxis due to delayed second-cycle parasite death at 1-3 µM serum concentrations. DOX concentrations >5 µM kill parasites with first-cycle activity but have been ascribed to off-target mechanisms outside the apicoplast.