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Tag: Dennis Kyle

Optimization of diastereomeric dihydropyridines as antimalarials

Donna Huber on June 18, 2024

The increase in research funding for the development of antimalarials since 2000 has led to a surge of new chemotypes with potent antimalarial activity. High-throughput screens have delivered several thousand new active compounds in several hundred series, including the 4,7-diphenyl-1,4,5,6,7,8-hexahydroquinolines, hereafter termed dihydropyridines (DHPs). We optimized the DHPs for antimalarial activity. Structure-activity relationship studies focusing …

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 …

The influence of oviposition status on measures of transmission potential in malaria-infected mosquitoes depends on sugar availability

Donna Huber on May 23, 2024

Background: Like other oviparous organisms, the gonotrophic cycle of mosquitoes is not complete until they have selected a suitable habitat to oviposit. In addition to the evolutionary constraints associated with selective oviposition behavior, the physiological demands relative to an organism’s oviposition status also influence their nutrient requirement from the environment. Yet, studies that measure transmission potential …

Extended blood stage sensitivity profiles of Plasmodium cynomolgi to doxycycline and tafenoquine, as a model for Plasmodium vivax

Donna Huber on April 8, 2024

Testing Plasmodium vivax antimicrobial sensitivity is limited to ex vivo schizont maturation assays, which preclude determining the IC50s of delayed action antimalarials such as doxycycline. Using Plasmodium cynomolgi as a model for P. vivax, we determined the physiologically significant delayed death effect induced by doxycycline [IC50(96 h), 1,401 ± 607 nM]. As expected, IC50(96 h) to chloroquine (20.4 nM), piperaquine (12.6 µM), and …

Two CTEGD faculty members receive Creative Research Awards

Donna Huber on April 4, 2024

Jessica Kissinger and Dennis Kyle received the Lamar Dodd Creative Research Award during UGA’s Honors Week. The award recognizes established investigators whose overall scholarly body of work has had a major impact on the field of study and has established the investigator’s international reputation as a leader in the field. Jessica Kissinger, Distinguished Research Professor …

In Vitro Antimalarial Activity of Trichothecenes against Liver and Blood Stages of Plasmodium Species

Donna Huber on January 23, 2024

Trichothecenes (TCNs) are a large group of tricyclic sesquiterpenoid mycotoxins that have intriguing structural features and remarkable biological activities. Herein, we focused on three TCNs (anguidine, verrucarin A, and verrucarol) and their ability to target both the blood and liver stages of Plasmodium species, the parasite responsible for malaria. Anguidine and verrucarin A were found to be …

Blood meals from ‘dead-end’ vertebrate hosts enhance transmission potential of malaria-infected mosquitoes

Donna Huber on November 30, 2023

Ingestion of an additional blood meal(s) by a hematophagic insect can accelerate development of several vector-borne parasites and pathogens. Most studies, however, offer blood from the same vertebrate host species as the original challenge (for e.g., human for primary and additional blood meals). Here, we show a second blood meal from bovine and canine hosts …

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 …