Drug Discovery Archives - Center for Tropical and Emerging Global Diseases

Structure-Guided Optimization of Novel Inhibitors of Plasmodium Lysyl-tRNA Synthetase with Multistage Activity against Malaria Parasites

Donna Huber on June 2, 2026

A fused dihydropyrrolidino-pyrimidine hit with low lipophilicity and excellent ligand efficiency was identified in a biochemical screen of the Global Health Chemical Diversity Library (GHCDL) against Plasmodium lysyl-tRNA synthetase (KRS). Structure-guided lead optimization delivered analogues with potent parasite growth inhibition, excellent biochemical and cellular selectivity (>1000-fold), and oral efficacy in the malaria NOD-scid-IL2Rγnull (SCID) mouse model. Structural …

Identification of an Orally Efficacious Imidazo[4,5- c]pyridine-6-Carboxamide Antimalarial with a High Barrier to Resistance

Donna Huber on April 27, 2026

Due to the emergence of resistance to both artemisinin derivatives, and their partner drugs, new antimalarials are urgently needed. Ideally, new orally active antimalarials would not only engage new targets but also demonstrate a high barrier to resistance selection, and the ability to kill both proliferating rings and growth-arrested rings resulting from artemisinin exposure. In …

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 …

Pharmacokinetic Analysis of Sustained-Release Buprenorphine Formulations in Owl Monkeys (Aotus spp.)

Donna Huber on September 24, 2025

Buprenorphine is an opioid used for pain management in veterinary medicine but which requires frequent dosing to maintain therapeutic levels. Sustained-release buprenorphine (BSR) formulations can overcome this limitation, but genera- or species-specific studies that determine the time profiles of buprenorphine after dosing are sparse for NHPs. The objective of this study was to determine the …

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 …

UGA researchers develop first test of cure for Chagas disease

Donna Huber on July 1, 2025

New test protocol can detect low levels of Trypanosoma cruzi, the parasite that causes Chagas disease Researchers at the University of Georgia’s Center for Tropical and Emerging Global Diseases have developed the first test to determine whether treatment for Chagas disease was effective. An estimated 6 million to 8 million people worldwide are infected with …

Chemical and Genetic Validation of an Essential Calcium Entry Channel of Trypanosoma brucei as a Therapeutic Target

Donna Huber on June 3, 2025

The Trypanosoma brucei group of parasites causes Nagana in cattle and human African trypanosomiasis, or sleeping sickness, in humans. Current drugs against these parasites have severe toxicity, vaccines are not available, and development of drug resistance makes finding new chemotherapeutic targets imperative. Ion channels, which are involved in several biological processes, are targets of many therapeutically useful …

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 …

Tag: Drug Discovery