University of Georgia
Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors

Tag: Belen Cassera

Characterization of β-Carboline Derivatives Reveals a High Barrier to Resistance and Potent Activity against Ring-Stage and DHA-Induced Dormant Plasmodium falciparum

Donna Huber on October 17, 2025

Malaria, caused by Plasmodium falciparum, remains a major global health challenge, with an estimated 263 million new infections and 597,000 deaths annually. Increasing resistance to current antimalarial drugs underscores the urgent need for new therapeutics that target novel pathways in the parasite. We previously reported a novel class of β-carboline antimalarials, exemplified by PRC1584, which demonstrated …

Benzo-ring modification on Malaria Box hit MMV008138: effects on antimalarial potency and microsomal stability

Donna Huber on August 15, 2025

Tetrahydro-β-carboline 1 (MMV008138) controls growth of asexual blood-stage Plasmodium falciparum by inhibiting IspD, an enzyme in the MEP pathway for synthesis of a critical metabolite, isopentenyl pyrophosphate (IPP). We have previously investigated the structure activity relationship (SAR) of three of its four rings (B, C, and D). In this report we investigate the SAR of …

Antimalarial spirooxindole alkaloids with a rare 6/5/5/6/6 polycyclic skeleton from the fungus Penicillium citrinum YSC-1 isolated from a medicinal plant

Donna Huber on August 5, 2025

OSMAC (one strain many compounds) provides a convenient strategy to produce chemically diverse and novel natural products. In the study, the application of an OSMAC approach on a fungus Penicillium citrinum YSC-1 isolated from a medicinal plant Chloranthus japonicus, using different culture media, led to the isolation and identification of seven new spirooxindole alkaloids penicitrimicins …

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 …

Spirocyclic iridoid alkaloids from Plumeria rubra

Donna Huber on December 13, 2024

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 …

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

Donna Huber on October 28, 2024

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 …

Aptamer-Based Imaging of Polyisoprenoids in the Malaria Parasite

Donna Huber on December 28, 2023

  Dolichols are isoprenoid end-products of the mevalonate and 2C-methyl-D-erythritol-4-phosphate pathways. The synthesis of dolichols is initiated with the addition of several molecules of isopentenyl diphosphate to farnesyl diphosphate. This reaction is catalyzed by a cis-prenyltransferase and leads to the formation of polyprenyl diphosphate. Subsequent steps involve the dephosphorylation and reduction of the α-isoprene unit …

All the pieces matter: UGA researchers collaborate to solve malaria puzzle

Donna Huber on April 25, 2023

Super-resolution microscopy showing malaria parasites infecting human red blood cells. credit: Muthugapatti Kandasamy, Biomedical Microscopy Core They say what doesn’t kill you makes you stronger. Whoever coined that adage had probably never heard of Plasmodium. It’s a microscopic parasite, invisible to the naked eye but common in tropical and subtropical regions throughout the world. Each …

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 …