A5051787175- Microbial Natural Products and Biosynthesis
- Antimicrobial Peptides and Activities
- Malaria Research and Control
- X-ray Diffraction in Crystallography
- Ubiquitin and proteasome pathways
- Crystallization and Solubility Studies
- Metabolomics and Mass Spectrometry Studies
- Synthesis and Catalytic Reactions
- Calcium signaling and nucleotide metabolism
- Bioactive Compounds and Antitumor Agents
- T-cell and B-cell Immunology
- Pharmacological Effects of Natural Compounds
- Toxoplasma gondii Research Studies
- Histone Deacetylase Inhibitors Research
- Biochemical and Structural Characterization
- Traditional and Medicinal Uses of Annonaceae
- Bacillus and Francisella bacterial research
- Vaccine Coverage and Hesitancy
- Immunodeficiency and Autoimmune Disorders
- Entomopathogenic Microorganisms in Pest Control
- Endoplasmic Reticulum Stress and Disease
- Adenosine and Purinergic Signaling
- Microtubule and mitosis dynamics
- Studies on Chitinases and Chitosanases
- Marine Sponges and Natural Products
University of Central Florida
2020-2025
Maricopa County Department of Public Health
2023
Nazareth College
2006
United States Department of Veterans Affairs
1988
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...
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...
Malaria remains a worldwide threat, afflicting over 200 million people each year. The emergence of drug resistance against existing therapeutics threatens to destabilize global efforts aimed at controlling Plasmodium spp. parasites, which is expected leave vast portions humanity unprotected the disease. To address this need, systematic testing fungal natural product extract library assembled through University Oklahoma Citizen Science Soil Collection Program has generated an initial set...
Select natural products are ideal starting points for ring distortion, or the dramatic altering of inherently complex molecules through short synthetic pathways, to generate an array novel compounds with diverse skeletal architectures. A major goal our distortion approach is re-engineer biological activity indole alkaloids identify new activities in areas significance human health and medicine. In this study, we re-engineered alkaloid yohimbine rearrangement cleavage synthesis pathways...
Xanthoquinodins make up a distinctive class of xanthone-anthraquinone heterodimers reported as secondary metabolites from several fungal species. Through collaborative multi-institutional screening program, extract prepared Trichocladium sp. was identified that exhibited strong inhibitory effects against human pathogens (Mycoplasma genitalium, Plasmodium falciparum, Cryptosporidium parvum, and Trichomonas vaginalis). This report focuses on one the unique samples desirable combination...
ABSTRACT In an effort to identify novel compounds with potent inhibition against Toxoplasma gondii, a phenotypic screen was performed utilizing library of 683 pure derived primarily from terrestrial and marine fungi. An initial fixed concentration 5 µM yielded 91 hits comparable equal artemisinin. These were then triaged based on known biological chemical concerns liabilities. From these, 49 prioritized tested in dose response format T. gondii human foreskin fibroblasts (HFFs) for...
Cyclic tetrapeptide histone deacetylase inhibitors represent a promising class of antiplasmodial agents that epigenetically disrupt wide range cellular processes in Plasmodium falciparum. Unfortunately, certain limitations, including reversible killing effects and host cell toxicity, prevented these from further development clinical use as antimalarials. In this study, we present series cyclic analogues derived primarily the fungus Wardomyces dimerus inhibit P. falciparum with low nanomolar...
There is an urgent need to develop new efficacious antimalarials address the emerging drug-resistant clinical cases. Our previous phenotypic screening identified styrylquinoline UCF501 as a promising antimalarial compound. To optimize UCF501, we herein report detailed structure–activity relationship study of 2-arylvinylquinolines, leading discovery potent, low nanomolar antiplasmodial compounds against Plasmodium falciparum CQ-resistant Dd2 strain, with excellent selectivity profiles...
Novel drug leads for malaria therapy are urgently needed because of the widespread emergence resistance to all available drugs. Screening Harbor Branch enriched fraction library against Plasmodium falciparum chloroquine-resistant strain (Dd2) followed by bioassay-guided fractionation led identification two potent antiplasmodials; a novel diterpene designated as bebrycin A (1) and known C21 degraded terpene nitenin (2). SYBR Green I assay was used establish Dd2 EC50 1.08 ± 0.21 0.29 0.02 µM...
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,...
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...
Background and Purpose. This article describes the implementation of a unique educational model for teaching management content explicitly utilizing experiential service learning principles. It also highlights physical therapist student faculty growth that have occurred in last 3 years as result implementing these strategies into program's curriculum. was developed an effort to meet Nazareth College mission community engagement, achieve program goals infusing more curricular integration...
Protein kinases have proven to be a very productive class of therapeutic targets, and over 90 inhibitors are currently in clinical use primarily for the treatment cancer. Repurposing these as antimalarials could provide an accelerated path drug development. In this study, we identified BI-2536, known potent human polo-like kinase 1 inhibitor, with low nanomolar antiplasmodial activity. Screening additional PLK1 revealed further candidates despite lack obvious orthologue PLKs Plasmodium. A...
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.
With increasing mpox cases in Maricopa County, Arizona, the county's health department launched a survey on July 11, 2022, to gather eligibility and contact data provide clinic information those interested JYNNEOS as postexposure prophylaxis (PEP) or expanded prophylaxis(PEP++). Survey were matched case vaccination data. Overall, 343 of 513 respondents (66.9%) who reported close with an patient received PEP 1712 3379 (50.7%) unsure their status PEP++. This outreach intervention connected...
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...