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Tag: malaria

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

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

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

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 …

Kurup wins prestigious PATH award for groundbreaking malaria research

Assistant Professor Samarchith “Sam” Kurup is the first UGA researcher to receive the Burroughs Wellcome Fund’s Investigators in Pathogenesis of Infectious Disease (PATH) award. Kurup studies the parasites that cause malaria and how they penetrate the body’s defenses, which could lead to more effective therapeutics. (Photo by Lauren Corcino) Every year, malaria evades the immune …

Regulatory T cell memory: implications for malaria

Regulatory T cells (Tregs) can persist as memory cells (mTregs) in both infectious and non-infectious settings. However, their functional behavior, phenotypic stability, and suppressive properties upon antigen re-exposure remain poorly understood. Emerging evidence suggests that mTregs exhibit enhanced proliferation and suppressive capacity upon re-encountering the same antigen, a feature that may be critical in recurrent …

Type I interferons induce guanylate-binding proteins and lysosomal defense in hepatocytes to control malaria

Plasmodium parasites undergo development and replication within hepatocytes before infecting erythrocytes and initiating clinical malaria. Although type I interferons (IFNs) are known to hinder Plasmodium infection within the liver, the underlying mechanisms remain unclear. Here, we describe two IFN-I-driven hepatocyte antimicrobial programs controlling liver-stage malaria. First, oxidative defense by NADPH oxidases 2 and 4 triggers …

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

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 …