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Tag: Drug Discovery

Discovery and optimization of a novel carboxamide scaffold with selective antimalarial activity

Donna Huber on March 28, 2025

Artemisinin combination therapies (ACTs) are critical components of malaria control worldwide. Alarmingly, ACTs have begun to fail, owing to the rise in artemisinin resistance. Thus, there is an urgent need for an expanded set of novel antimalarials to generate new combination therapies. Herein, we have identified a 1,2,4-triazole-containing carboxamide scaffold that, through scaffold hopping efforts, …

Stereospecific Resistance to N2-Acyl Tetrahydro-β-carboline Antimalarials Is Mediated by a PfMDR1 Mutation That Confers Collateral Drug Sensitivity

Donna Huber on January 14, 2025

Half the world’s population is at risk of developing a malaria infection, which is caused by parasites of the genus Plasmodium. Currently, resistance has been identified to all clinically available antimalarials, highlighting an urgent need to develop novel compounds and better understand common mechanisms of resistance. We previously identified a novel tetrahydro-β-carboline compound, PRC1590, which …

A kalihinol analog disrupts apicoplast function and vesicular trafficking in P. falciparum malaria

Donna Huber on September 27, 2024

  We report the discovery of MED6-189, an analog of the kalihinol family of isocyanoterpene natural products that is effective against drug-sensitive and drug-resistant Plasmodium falciparum strains, blocking both asexual replication and sexual differentiation. In vivo studies using a humanized mouse model of malaria confirm strong efficacy of the compound in animals with no apparent hemolytic activity …

A Drug Repurposing Approach Reveals Targetable Epigenetic Pathways in Plasmodium vivax Hypnozoites

Donna Huber on May 29, 2024

Radical cure of Plasmodium vivax malaria must include elimination of quiescent ‘hypnozoite’ forms in the liver; however, the only FDA-approved treatments are contraindicated in many vulnerable populations. To identify new drugs and drug targets for hypnozoites, we screened the Repurposing, Focused Rescue, and Accelerated Medchem (ReFRAME) library and a collection of epigenetic inhibitors against P. vivax liver stages. From …

UGA researchers received prestigious grant to develop malaria drug

Donna Huber on October 12, 2023

by Amy Horton   New compound targets P. vivax, source of recent U.S. infections Two University of Georgia researchers have been awarded approximately $770,000 from the Global Health Initiative Technology (GHIT) Fund to develop a new drug to kill the dormant liver stages of Plasmodium vivax, the most widespread of the malaria parasites. This amount …

Sheptide A: an antimalarial cyclic pentapeptide from a fungal strain in the Herpotrichiellaceae

Donna Huber on September 20, 2023

As part of ongoing efforts to isolate biologically active fungal metabolites, a cyclic pentapeptide, sheptide A (1), was discovered from strain MSX53339 (Herpotrichiellaceae). The structure and sequence of 1 were determined primarily by analysis of 2D NMR and HRMS/MS data, while the absolute configuration was assigned using a modified version of Marfey’s method. In an …

Effective drug discovery in Chagas disease

Donna Huber on May 15, 2023

The Chagas field has gone >50 years without tangible progress toward new therapies. My colleagues and I have recently reported on a benzoxaborole compound that achieves consistent parasitological cure in experimentally infected mice and in naturally infected non-human primates (NHPs). While these results do not assure success in human clinical trials, they significantly de-risk this …

Identification of novel anti-amoebic pharmacophores from kinase inhibitor chemotypes

Donna Huber on May 10, 2023

Acanthamoeba species, Naegleria fowleri, and Balamuthia mandrillaris are opportunistic pathogens that cause a range of brain, skin, eye, and disseminated diseases in humans and animals. These pathogenic free-living amoebae (pFLA) are commonly misdiagnosed and have sub-optimal treatment regimens which contribute to the extremely high mortality rates (>90%) when they infect the central nervous system. To address the unmet medical …

Cripowellins Pause Plasmodium falciparum Intraerythrocytic Development at the Ring Stage

Donna Huber on March 13, 2023

  Cripowellins from Crinum erubescens are known pesticidal and have potent antiplasmodial activity. To gain mechanistic insights to this class of natural products, studies to determine the timing of action of cripowellins within the asexual intraerythrocytic cycle of Plasmodium falciparum were performed and led to the observation that this class of natural products induced reversible cytostasis in the ring …