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Tag: malaria

Expeditious recruitment of circulating memory CD8 T cells to the liver facilitates control of malaria

Donna Huber on November 2, 2021

Circulating memory CD8 T cell trafficking and protective capacity during liver-stage malaria infection remains undefined. We find that effector memory CD8 T cells (Tem) infiltrate the liver within 6 hours after malarial or bacterial infections and mediate pathogen clearance. Tem recruitment coincides with rapid transcriptional upregulation of inflammatory genes in Plasmodium-infected livers. Recruitment requires CD8 …

Researchers implement new tool to screen drugs for treating malaria relapses

Donna Huber on October 21, 2021

Steve Maher, assistant research scientist in the Center for Tropical Emerging and Global Diseases, leads a team of researchers who have implemented a new screening tool to determine if a drug candidate kills hypnozoites, the cause of malaria relapses. (Photo by Donna Huber) Globally, efforts to control malaria caused by Plasmodium vivax are lagging behind that of …

Probing the distinct chemosensitivity of Plasmodium vivax liver stage parasites and demonstration of 8-aminoquinoline radical cure activity in vitro

Donna Huber on October 7, 2021

Improved control of Plasmodium vivax malaria can be achieved with the discovery of new antimalarials with radical cure efficacy, including prevention of relapse caused by hypnozoites residing in the liver of patients. We screened several compound libraries against P. vivax liver stages, including 1565 compounds against mature hypnozoites, resulting in one drug-like and several probe-like …

UGA researchers developing new models for malaria drug development and testing

Donna Huber on September 23, 2021

CTEGD member Chet Joyner and CTEGD director Dennis Kyle receive a grant from the Bill & Melinda Gates Foundation for malaria drug development and testing Two UGA researchers are working to make it easier to develop effective treatments for malaria, a disease that sickens millions worldwide and kills hundreds of thousands each year. In tropical …

Researchers to test drug candidates to treat malaria

Donna Huber on September 15, 2021

by Donna Huber Belen Cassera is leading a research team that will test two new drugs for the treatment of malaria. The team's work will be funded by a $3.7 million grant from the National Institutes of Health. (Photo credit: Amy Ware) Though malaria was eliminated from the U.S. 70 years ago, the mosquito-borne disease …

Aminoalkoxycarbonyloxymethyl Ether Prodrugs with a pH-Triggered Release Mechanism: A Case Study Improving the Solubility, Bioavailability, and Efficacy of Antimalarial 4(1 H)-Quinolones with Single Dose Cures

Donna Huber on May 12, 2021

Preclinical and clinical development of numerous small molecules is prevented by their poor aqueous solubility, limited absorption, and oral bioavailability. Herein, we disclose a general prodrug approach that converts promising lead compounds into aminoalkoxycarbonyloxymethyl (amino AOCOM) ether-substituted analogues that display significantly improved aqueous solubility and enhanced oral bioavailability, restoring key requirements typical for drug candidate …

Some conditions apply: Systems for studying Plasmodium falciparum protein function

Donna Huber on April 22, 2021

Fig 1. Conditional protein knockdown used throughout the Plasmodium falciparum life cycle. Malaria, caused by infection with Plasmodium parasites, remains a significant global health concern. For decades, genetic intractability and limited tools hindered our ability to study essential proteins and pathways in Plasmodium falciparum, the parasite associated with the most severe malaria cases. However, recent …

Synthesis of Mono- and Bisperoxide-Bridged Artemisinin Dimers to Elucidate the Contribution of Dimerization to Antimalarial Activity

Donna Huber on April 1, 2021

During the past decade, artemisinin as an antimalarial has been in the spotlight, in part due to the Nobel Prize in Physiology or Medicine awarded to Tu Youyou. While many studies have been completed detailing the significant increase in activity resulting from the dimerization of natural product artemisinin, activity increases unaccounted for by the peroxide …

A redox-active crosslinker reveals an essential and inhibitable oxidative folding network in the endoplasmic reticulum of malaria parasites

Donna Huber on February 3, 2021

Malaria remains a major global health problem, creating a constant need for research to identify druggable weaknesses in P. falciparum biology. As important components of cellular redox biology, members of the Thioredoxin (Trx) superfamily of proteins have received interest as potential drug targets in Apicomplexans. However, the function and essentiality of endoplasmic reticulum (ER)-localized Trx-domain …

Resistance to some, but not other dimeric lindenane sesquiterpenoid esters is mediated by mutations in a Plasmodium falciparum esterase

Donna Huber on September 24, 2020

Unique lindenane sesquiterpenoid dimers from Chloranthecae spp. were recently identified with promising in vitro antiplasmodial activity and potentially novel mechanisms of action. To gain mechanistic insights to this new class of natural products, in vitro selection of Plasmodium falciparum resistance to the most active antiplasmodial compound, chlorajaponilide C, was explored. In all selected resistant clones, …