APEX2-based proximity proteomic analysis identifies candidate interactors for Plasmodium falciparum knob-associated histidine-rich protein in infected erythrocytes.

The interaction of Plasmodium falciparum-infected red blood cells (iRBCs) with the vascular endothelium plays a crucial role in malaria pathology and disease. KAHRP is an exported P. falciparum protein involved in iRBC remodelling, which is essential for the formation of protrusions or "knobs" on the iRBC surface.

Synthesis of Novel Artemisinin, Ciprofloxacin, and Norfloxacin Hybrids with Potent Antiplasmodial Activity.

The synthesis and antiplasmodial evaluation of new hybrids combining the pharmacophore structures of artemisinin, ciprofloxacin or norfloxacin, and 7-chloroquinoline are reported in this study. The first step for all of the syntheses is the obtainment of key piperazine esters intermediates bearing the drugs ciprofloxacin and norfloxacin. Using these platforms, 18 final compounds were synthesized through a multistep procedure with overall yields ranging between 8 and 20%.

The ethnopharmacological study of plant drugs used traditionally in Djibouti for malaria treatment.

Ethnopharmacological Relevance: Djibouti was a country where malaria has been endemic for centuries. The local population use the plants as repellents or first aid for uncomplicated malaria.

Aim Of The Study: The aim was, for the first time, to collect and identify plants used by the local population to treat malaria and select the most interesting plants (those that are more commontly used, more available, and have fewer studies).

Multitask learning-driven identification of novel antitrypanosomal compounds.

Chagas disease and human African trypanosomiasis cause substantial death and morbidity, particularly in low- and middle-income countries, making the need for novel drugs urgent. Therefore, an explainable multitask pipeline to profile the activity of compounds against three trypanosomes ( and ) were created. These models successfully discovered four new experimental hits (, , and ).

Insights into the microRNA landscape of Rhodnius prolixus, a vector of Chagas disease.

The growing interest in microRNAs (miRNAs) over recent years has led to their characterization in numerous organisms. However, there is currently a lack of data available on miRNAs from triatomine bugs (Reduviidae: Triatominae), which are the vectors of the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease. A comprehensive understanding of the molecular biology of vectors provides new insights into insect-host interactions and insect control approaches, which are key methods to prevent disease incidence in endemic areas.

From the Spectroscopic Reassessment of Authentic Alkaloid Samples to the Molecular Networking-Guided Discovery of Criophylline-Related Analogues from .

The molecular network-guided exploration of the alkaloid extract of stems revealed a cluster attributed tentatively to dimeric monoterpene indole alkaloids of the rare criophylline subtype, initiating the dual study reported herein. A patrimonial-themed portion of this work was aimed at performing a spectroscopic reassessment of criophylline (), a monoterpene bisindole alkaloid for which the nature of the inter-monomeric connectivity and configurational assignments have remained dubious. A targeted isolation of the entity annotated as criophylline () was undertaken to strengthen the available analytical evidence.

Identification of novel Zika virus NS3 protease inhibitors with different inhibition modes by integrative experimental and computational approaches.

Zika virus (ZIKV) infection is associated with severe neurological disorders and congenital malformation. Despite efforts to eradicate the disease, there is still neither vaccine nor approved drugs to treat ZIKV infection. The NS2B-NS3 protease is a validated drug target since it is essential to polyprotein virus maturation.

Biodereplication of Antiplasmodial Extracts: Application of the Amazonian Medicinal Plant Kunth.

Improved methodological tools to hasten antimalarial drug discovery remain of interest, especially when considering natural products as a source of drug candidates. We propose a biodereplication method combining the classical dereplication approach with the early detection of potential antiplasmodial compounds in crude extracts. Heme binding is used as a surrogate of the antiplasmodial activity and is monitored by mass spectrometry in a biomimetic assay.

Robust inactivation of Plasmodium falciparum in red blood cell concentrates using amustaline and glutathione pathogen reduction.

Background: Plasmodium falciparum is the parasite responsible for most malaria cases globally. The risk of transfusion-transmitted malaria (TTM) is mitigated by donor deferrals and blood screening strategies, which adversely impact blood availability. Previous studies showed robust inactivation of P.

Antiparasitic Ovalicin Derivatives from , a Mutualistic Fungus of French Guiana Termites.

Social insects are in mutualism with microorganisms, contributing to their resistance against infectious diseases. The fungus SNB-CN85 isolated from termites produces ovalicin derivatives resulting from the esterification of the less hindered site of the ovalicin epoxide by long-chain fatty acids. Their structures were elucidated using spectroscopic analysis and semisynthesis from ovalicin.

Calcium in the Backstage of Malaria Parasite Biology.

The calcium ion (Ca) is a ubiquitous second messenger involved in key biological processes in prokaryotes and eukaryotes. In species, Ca signaling plays a central role in the parasite life cycle. It has been associated with parasite development, fertilization, locomotion, and host cell infection.

Role of human group IIA secreted phospholipase A2 in malaria pathophysiology: Insights from a transgenic mouse model.

We previously showed that injection of recombinant human group IIA secreted phospholipase A (hGIIA sPLA) to Plasmodium chabaudi-infected mice lowers parasitaemia by 20%. Here, we show that transgenic (TG) mice overexpressing hGIIA sPLA have a peak of parasitaemia about 30% lower than WT littermates. During infection, levels of circulating sPLA, enzymatic activity and plasma lipid peroxidation were maximal at day-14, the peak of parasitaemia.

Targeted Isolation of Hemitheion from , a Proposed Biosynthetic Intermediate of Theionbrunonines.

Hemitheion (), a new sulfur-containing vobasane-type indole alkaloid, was isolated, together with three known compounds, vobasine (), gelsedine (), and gelsemicine (), from the alkaloid extract of the stems of Didr. (Gelsemiaceae). Compound could be straightforwardly isolated.

Comparative proteomic analysis of kinesin-8B deficient Plasmodium berghei during gametogenesis.

Plasmodium blood stages, responsible for human to vector transmission, termed gametocytes, are the precursor cells that develop into gametes in the mosquito. Male gametogenesis works as a bottleneck for the parasite life cycle, where, during a peculiar and rapid exflagellation, a male gametocyte produces 8 intracellular axonemes that generate by budding 8 motile gametes. Understanding the molecular mechanisms of gametogenesis is key to design strategies for controlling malaria transmission.

A Photoalkylative Fluorogenic Probe of Guttiferone A for Live Cell Imaging and Proteome Labeling in .

Guttiferone A (GA) , a polycyclic polyprenylated acylphloroglucinol (PPAP) isolated from the plant (Clusiaceae), constitutes a novel hit in antimalarial drug discovery. PPAPs do not possess identified biochemical targets in malarial parasites up to now. Towards this aim, we designed and evaluated a natural product-derived photoactivatable probe AZC-GA , embedding a photoalkylative fluorogenic motif of the 7-azidocoumarin (AZC) type, devoted to studying the affinity proteins interacting with GA in .

Synthesis and Antiplasmodial Activity of Novel Fosmidomycin Derivatives and Conjugates with Artemisinin and Aminochloroquinoline.

Malaria, despite many efforts, remains among the most problematic infectious diseases worldwide, mainly due to the development of drug resistance by The antibiotic fosmidomycin (FSM) is also known for its antimalarial activity by targeting the non-mevalonate isoprenoid synthesis pathway, which is essential for the malaria parasites but is absent in mammalians. In this study, we synthesized and evaluated against the chloroquine-resistant strain, a series of FSM analogs, derivatives, and conjugates with other antimalarial agents, such as artemisinin (ART) and aminochloroquinoline (ACQ). The biological evaluation revealed four new compounds with higher antimalarial activity than FSM: two FSM-ACQ derivatives and two FSM-ART conjugates, with 3.

Streamlined targeting of Amaryllidaceae alkaloids from the bulbs of Crinum scillifolium using spectrometric and taxonomically-informed scoring metabolite annotations.

Four undescribed alkaloids have been isolated from the bulbs of the previously unstudied Crinum scillifolium. These compounds were targeted following a state-of-the-art molecular networking strategy comprising a dereplication against in silico databases and re-ranking of the candidate structures based on taxonomically informed scoring. The unreported structures span across a variety of Amaryllidaceae alkaloids appendages.

Analysing ambiguities in trypanosomatids taxonomy by barcoding.

Background: Biodiversity screens and phylogenetic studies are dependent on reliable DNA sequences in public databases. Biological collections possess vouchered specimens with a traceable history. Therefore, DNA sequencing of samples available at institutional collections can greatly contribute to taxonomy, and studies on evolution and biodiversity.

Prolyl Oligopeptidase From : Biochemical Characterization and Involvement in Macrophage Infection.

is a flagellated protozoan and one of the main causative agents of visceral leishmaniasis. This disease usually affects the human reticuloendothelial system, can cause death and available therapies may lead to serious side effects. Since it is a neglected tropical disease, the incentives for the development of new drugs are insufficient.

Corynanthean-Epicatechin Flavoalkaloids from .

Epicatechocorynantheines A and B, and epicatechocorynantheidine were isolated from the stem bark of . These molecules were pinpointed, and their isolation streamlined, by a molecular networking strategy. The structural elucidation was unambiguously accomplished from HRMS and 1D/2D NMR data.

Synthesis of Novel G Factor or Chloroquine-Artemisinin Hybrids and Conjugates with Potent Antiplasmodial Activity.

A series of novel hybrids of artemisinin (ART) with either a phytormone endoperoxide G factor analogue (GMeP) or chloroquine (CQ) and conjugates of the same compounds with the polyamines (PAs), spermidine (Spd), and homospermidine (Hsd) were synthesized and their antiplasmodial activity was evaluated using the CQ-resistant FcB1/Colombia strain. The ART-GMeP hybrid and compounds and which are conjugates of Spd and Hsd with two molecules of ART and one molecule of GMeP, were the most potent with IC values of 2.6, 8.

Inactivation of Plasmodium falciparum in whole blood using the amustaline and glutathione pathogen reduction technology.

Background: Risk of transfusion-transmitted (TT) malaria is mainly associated with whole blood (WB) or red blood cell (RBC) transfusion. Risk mitigation relies mostly on donor deferral while a limited number of countries perform blood testing, both negatively impacting blood availability. This study investigated the efficacy of the pathogen reduction system using amustaline and glutathione (GSH) to inactivate Plasmodium falciparum in WB.

Molecular Networking Reveals Serpentinine-Related Bisindole Alkaloids from , a Previously Well-Investigated Species.

Five new monoterpene indole alkaloids (-), including four serpentinine-related bisindoles and one alstonine derivative monomer, have been isolated from the aerial parts of . Their structures were elucidated by analysis of their HRMS and NMR spectroscopic data, and their absolute configurations were deduced from the comparison of experimental and simulated ECD spectra. In addition, two known compounds ( and ), previously undescribed from , have also been purified.