Raphaella Paes

ORCID: 0000-0002-6146-5309
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Research Areas
  • Microbial Natural Products and Biosynthesis
  • Calcium signaling and nucleotide metabolism
  • Metabolomics and Mass Spectrometry Studies
  • Entomopathogenic Microorganisms in Pest Control
  • Alkaloids: synthesis and pharmacology
  • Oxidative Organic Chemistry Reactions
  • Antimicrobial Peptides and Activities
  • Mass Spectrometry Techniques and Applications
  • Plant Pathogens and Fungal Diseases
  • Bioactive Compounds and Antitumor Agents
  • Pharmacological Effects of Natural Compounds
  • Moringa oleifera research and applications
  • Lipid Membrane Structure and Behavior
  • Mycorrhizal Fungi and Plant Interactions
  • Fungal Biology and Applications
  • Pharmacological Receptor Mechanisms and Effects
  • Adenosine and Purinergic Signaling
  • Genomics and Phylogenetic Studies
  • Berberine and alkaloids research
  • Studies on Chitinases and Chitosanases

University of Central Florida
2022-2025

Abstract Cryptosporidium is a common, waterborne gastrointestinal parasite that causes diarrheal disease worldwide. Currently there are no effective therapeutics to treat cryptosporidiosis in at-risk populations. Since natural products known source of anti-parasitic compounds, we screened library extracts and pure product compounds isolated from bacteria fungi collected subterranean environments for activity against parvum . Eight structurally related norditerpene lactones the fungus...

10.1101/2025.01.02.631097 preprint EN cc-by-nc-nd bioRxiv (Cold Spring Harbor Laboratory) 2025-01-03

Herein we report the finding and structure determination of a natural product based on methyldeoxaphomin scaffold family from fungus Trichocladium asperum that shows promising antiplasmodial activity selectivity against host cells. In vitro evolution whole genome analysis in Plasmodium falciparum with most potent member, NPDG-F (EC 50 550 nM Dd2; 290 3D7), parasite resistance to methyldeoxaphomins is strongly associated mutations PfActin1 (PF3D7_1246200), critically essential ATPase needed...

10.1073/pnas.2418871122 article EN cc-by Proceedings of the National Academy of Sciences 2025-02-18

ABSTRACT Natural products are a critical source of novel chemotypes for drug discovery. However, the implementation natural product extract libraries in high throughput screening is hampered by structural redundancy and potential bioactive re-discovery. This challenge large library sizes drastically increase time cost during initial screens. To address these limitations, we developed method that leverages liquid chromatography-tandem mass spectrometry spectral similarity to dramatically...

10.1128/msystems.00844-24 article EN cc-by mSystems 2025-02-24

Our previous study identified 52 antiplasmodial peptaibols isolated from fungi. To understand their mechanism of action, we conducted phenotypic assays, assessed the in vitro evolution resistance, and performed a transcriptome analysis most potent peptaibol, HZ NPDG-I. NPDG-I 2 additional were compared for killing action stage dependency, each showing loss digestive vacuole (DV) content via ultrastructural analysis. demonstrated stepwise increase DV pH, impaired membrane permeability,...

10.1016/j.chembiol.2023.10.025 article EN cc-by Cell chemical biology 2023-11-22

Our previous work identified a series of 12 xanthoquinodin analogues and 2 emodin-dianthrones with broad-spectrum activities against Trichomonas vaginalis, Mycoplasma genitalium, Cryptosporidium parvum, Plasmodium falciparum. Analyses conducted in this study revealed that the most active analogue, A1, also inhibits Toxoplasma gondii tachyzoites liver stage berghei, no cross-resistance to known antimalarial targets PfACS, PfCARL, PfPI4K, or DHODH. In Plasmodium, inhibition occurs prior...

10.1021/acsinfecdis.4c00232 article EN ACS Infectious Diseases 2024-05-29

Natural product libraries are crucial to drug development, but large drastically increase the time and cost during initial high throughput screens. Here, we developed a method that leverages liquid chromatography-tandem mass spectrometry spectral similarity dramatically reduce library size, with minimal bioactive loss. This offers broadly applicable strategy for accelerated discovery reductions, which enable implementation in resource-limited settings.

10.1101/2024.05.22.595232 preprint EN cc-by-nd bioRxiv (Cold Spring Harbor Laboratory) 2024-05-26

Natural product ring distortion strategies have enabled rapid access to unique libraries of stereochemically complex compounds explore new chemical space and increase our understanding biological processes related human disease. Herein is described the development a ring-cleavage strategy using indole alkaloids yohimbine, apovincamine, vinburnine, reserpine that were reacted with diversity chloroformates paired various alcohol/thiol nucleophiles enable synthesis 47 novel small molecules....

10.1039/d4ob00853g article EN Organic & Biomolecular Chemistry 2024-01-01

Our previous study identified 52 antiplasmodial peptaibols isolated from Trichoderma and Hypocrea fungal species. To understand their mechanism of action, we conducted phenotypic assays, in vitro evolution resistance, transcriptome analysis the most potent peptaibol, harzianin NPDG I (HZ NPDG-I). This, two additional were compared for both killing action stage dependency, each showing a loss digestive vacuole (DV) content ultrastructural analysis. HZ-NPDG-I demonstrated stepwise increase DV...

10.2139/ssrn.4271103 article EN SSRN Electronic Journal 2022-01-01
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