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Author: Donna Huber

Spirocyclic iridoid alkaloids from Plumeria rubra

Plumerianoids A-D (1-4) with a new intact spirocyclic iridoid alkaloid skeleton, along with a new degraded alkaloid 8-epi-plumerianine (5), and a known one (6), were isolated and characterized from Plumeria rubra. The structure of 6 was revised as (8R,13S)-plumerianine. These alkaloids consist of three epimeric pairs (1/2, 3/4, and 5/6), exhibiting virtually identical NMR spectra within …

The Toxoplasma gondii homolog of ATPase inhibitory factor 1 is critical for mitochondrial cristae maintenance and stress response

The production of energy in the form of ATP by the mitochondrial ATP synthase must be tightly controlled. One well-conserved form of regulation is mediated via ATPase inhibitory factor 1 (IF1), which governs ATP synthase activity and gene expression patterns through a cytoprotective process known as mitohormesis. In apicomplexans, the processes regulating ATP synthase activity …

A pathway for skin NTD diagnostic development

  The present document outlines the next steps recommended by the Skin NTDs subgroup of the DTAG to operationalise individual disease TPPs and to advance the NTD road map approach of scaling up integrated approaches to skin NTDs. Michael Marks, Sundeep Chaitanya Vedithi, Wendy W J van de Sande, Bruno Levecke, Anthony W Solomon, Kingsley …

Screening the Global Health Priority Box against Plasmodium berghei liver stage parasites using an inexpensive luciferase detection protocol

Background: Malaria, a disease caused by parasites of the genus Plasmodium, continues to impact many regions globally. The rise in resistance to artemisinin-based anti-malarial drugs highlights the need for new treatments. Ideally, new anti-malarials will kill the asymptomatic liver stages as well as the symptomatic blood stages. While blood stage screening assays are routine and efficient, …

β-Carboline-3-carboxamide Antimalarials: Structure-Activity Relationship, ADME-Tox Studies, and Resistance Profiling

The development of parasite resistance to both artemisinin derivatives and their partner drugs jeopardizes the effectiveness of the artemisinin combination therapy. Thus, the discovery of new antimalarial drugs, with new mechanisms of action, is urgently needed. We recently disclosed that β-carboline 1a was orally efficacious in Plasmodium berghei-infected mice and that it showed low cross-resistance …

A myeloid differentiation-like protein in partnership with Toll5 from the pest insect Spodoptera litura senses baculovirus infection

  Many types of viruses infect insects and other arthropods. In contrast, little is known about how arthropods sense viruses, although several innate immune pathways including Toll have antiviral functions. Large DNA viruses in the family Baculoviridae are used to control a number of pest insects. Here, we studied Spodoptera litura and Autographa californica multiple nucleopolyhedrovirus (AcMNPV) to test …

Lipophilic bisphosphonates reduced cyst burden and ameliorated hyperactivity of mice chronically infected with Toxoplasma gondii

The current treatments for toxoplasmosis are only active against fast-growing tachyzoites, present in acute infections, with little effect on slow-growing bradyzoites within tissue cysts, present in latent chronic infections. The mitochondrion of Toxoplasma gondii is essential for its survival, and one of the major anti-parasitic drugs, atovaquone, inhibits the mitochondrial electron transport chain at the coenzyme Q:cytochrome …