A5081610788- Malaria Research and Control
- Marine Sponges and Natural Products
- Synthesis and biological activity
- Computational Drug Discovery Methods
- Phenothiazines and Benzothiazines Synthesis and Activities
- Chemical Synthesis and Analysis
- Synthesis and Biological Activity
- Microbial Natural Products and Biosynthesis
- Autophagy in Disease and Therapy
- Synthesis and Catalytic Reactions
- Biochemical and Molecular Research
- Endoplasmic Reticulum Stress and Disease
- Traditional and Medicinal Uses of Annonaceae
- Quinazolinone synthesis and applications
- Mosquito-borne diseases and control
- Parasite Biology and Host Interactions
- Antimicrobial Peptides and Activities
University of Central Florida
2013-2023
Drugs against malaria are losing their effectiveness because of emerging drug resistance. This underscores the need for novel therapeutic options with mechanism actions distinct from current antimalarials. To identify pharmacophores we have screened compounds containing structural features natural products that pharmacologically relevant. screening has identified a 4-nitro styrylquinoline (SQ) compound submicromolar antiplasmodial activity and excellent selectivity. SQ exhibits cellular...
A deep-water sponge of the genus Spongosorites has yielded a bis-indole alkaloid which we have named dragmacidin G. Dragmacidin G was first reported by us in patent literature and recently been Hitora et al. from Lipastrotheya. is this series compounds to pyrazine ring linking two indole rings. It also rare N-(2-mercaptoethyl)-guanidine side chain. shows broad spectrum biological activity including inhibition methicillin-resistant Staphylococcus aureus, Mycobacterium tuberculosis, Plasmodium...
PfPK7 is an "orphan" kinase displaying regions of homology to multiple protein families. functions in regulating parasite proliferation/development as evident from the phenotype analysis knockout parasites. Despite this regulatory role, signaling pathways are not known. To better understand PfPK7-regulated phosphorylation events, we performed isobaric tag-based quantitative comparative phosphoproteomics schizont and segmenter stages wild-type pfpk7- lines. This identified 3,875 sites on...
A library of enriched marine natural product fractions was screened for their antiplasmodial activity using a SYBR green I fluorescence-based assay. Fractions derived from sponge the genus Spongosorites exhibited potent inhibition Plasmodium falciparum growth. This has been reported to contain nortopsentin and topsentin class bis-indole imidazole alkaloids. is first report inhibiting parasite growth at trophozoite stage submicromolar 50% inhibitory concentrations (IC(50)).
We screened a collection of synthetic compounds consisting natural-product-like substructural motifs to identify spirocyclic chromane as novel antiplasmodial pharmacophore using an unbiased cell-based assay. The most active compound UCF 201 exhibits 50% effective concentration (EC50) 350 nM against the chloroquine-resistant Dd2 strain and selectivity over 50 human liver HepG2 cells. Our analyses physicochemical properties showed that it is in compliance with Lipinski's parameters has...
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...
The screening of more than 30 million compounds derived from 81 small molecule libraries built on distinct scaffolds identified pyrrolidine bis-cyclic guanidine library (TPI-1955) to be one the most active and selective antiplasmodial libraries. positional scanning TPI-1955 arranged four sets sublibraries (26 + 26 40), totaling 120 samples for testing provided information about important groups each variable position in containing 738,192 unique compounds. parallel synthesis individual...
It is important to discover novel antimalarial pharmacophores because of the widespread emergence Plasmodium falciparum isolates resistant available drugs. Secondary metabolites derived from microbes associated with marine invertebrates are a valuable resource for discovery drug leads. However, potential as source antimalarials has not been explored. We investigated promise microorganisms production activities by testing 2365 diverse microbial extracts using phenotypic screening multidrug...
Thiazole and piperazine are two important heterocyclic rings that play a prominent role in nature have broad range of applications agricultural medicinal chemistry. Herein, we report the parallel synthesis library diverse piperazine-tethered thiazole compounds. The reaction with newly generated 4-chloromethyl-2-amino thiazoles led to desired compounds high purities good overall yields. Using variety commercially available carboxylic acids, disubstituted...