Research Capacity Core – Tropical and Emerging Diseases Core
Research Areas
- Molecular mechanisms of drug resistance in Plasmodium
- Role of glutathione metabolism genes in parasite development (vertebrate & mosquito hosts)
- Drug target identification and validation in Plasmodium
- Discovery and evaluation of novel anti-Plasmodium compounds and natural products for potential therapeutic development
Scientific Achievements
- Identification of genes and mechanisms underlying Plasmodium drug resistance.
- Discovery and validation of Glutathione-S-Transferase (GST) as a novel antimalarial drug target led to screening of over 4 million compounds and secured two patents
- Patent PCT/US2020/017505 Compounds with Antimalarial Activity
- Patent USPTO 10,744,119 Novel Inhibitors of the Malarial GST
- Discovered novel compounds and natural compounds with potent antiplasmodial activity.
- Registration of a Machine Learning Tool to predict drug interactions (Roche-Lima & Serrano) MLSyPred – Machine Learning Synergy Predictor for drug combination therapies (Certificate of Registration TXu 2-263-404)
Funding
RCMI Funding:
- NIH/NIMHD U54MD007600
Other funding obtained with RCMI support:
- PRSTRT Grant; Novel inhibitors of the malarial GST – from bench to a marketable drug
- Identification and evaluation of SARS-CoV-2 cell entry inhibitors as novel drugs for COVID-19.
- SO6 NIGMS-SCORE Molecular mechanisms of multidrug resistance in rodent malaria
Scientific Advance
Novel hydrazone compounds with broad-spectrum antiplasmodial activity and synergistic interactions with antimalarial drugs.
Published in Antimicrobial Agents and Chemotherapy, Volume 68, 2025, PMCID: PMC12071843.
Published in Antimicrobial Agents and Chemotherapy, Volume 68, 2025, PMCID: PMC12071843.
The researchers tested seven new hydrazone-based compounds (named CB-27, CB-41, CB-50, CB-53, CB-58, CB-59, CB-61) to see how well they can kill or inhibit Plasmodium parasites, including resistant strains. They found that all compounds worked in blood stages of P. falciparum, with some (like CB-27 and CB-61) particularly potent. One compound (CB-41) also showed effectiveness in liver stages and in preventing infection in mosquito stages. Some compounds acted synergistically (worked better together) with known antimalarial drugs like clindamycin and halofantrine. Importantly, they didn’t show significant toxicity in tested human liver cells, which suggests promise for future drug development.
U54 MD007600/NIMHD NIH HHS/United States, AI001250-01 NIH /Division of Intramural Research, R25 GM061151/NIGMS NIH HHS/United States, 5R25GM061151-22/NIH National Institute of General Medical Sciences
