A5089506099- Marine Sponges and Natural Products
- Chemical Synthesis and Analysis
- Microbial Natural Products and Biosynthesis
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Reservoir Engineering and Simulation Methods
- Marine Biology and Environmental Chemistry
- Drilling and Well Engineering
- Biochemical Analysis and Sensing Techniques
- Biochemical and Structural Characterization
- Antimicrobial Peptides and Activities
- Clostridium difficile and Clostridium perfringens research
- Metabolomics and Mass Spectrometry Studies
- Cancer therapeutics and mechanisms
- Epigenetics and DNA Methylation
- Hydraulic Fracturing and Reservoir Analysis
- Pharmacological Effects of Natural Compounds
- Oil and Gas Production Techniques
- Phytochemical Studies and Bioactivities
- Herbal Medicine Research Studies
- Histone Deacetylase Inhibitors Research
- Natural product bioactivities and synthesis
- Genomics and Chromatin Dynamics
- Insect-Plant Interactions and Control
- Protein Degradation and Inhibitors
St. Jude Children's Research Hospital
2016-2024
University of Mississippi
2004-2014
Suez Canal University
2008
Weatherford College
2007
Chimeric transcription factors drive lineage-specific oncogenesis but are notoriously difficult to target. Alveolar rhabdomyosarcoma (RMS) is an aggressive childhood soft tissue sarcoma transformed by the pathognomonic Paired Box 3–Forkhead O1 (PAX3-FOXO1) fusion protein, which governs a core regulatory circuitry factor network. Here, we show that histone lysine demethylase 4B (KDM4B) therapeutic vulnerability for PAX3-FOXO1 + RMS. Genetic and pharmacologic inhibition of KDM4B substantially...
Aaptamine has potent cytotoxicity that may be explained by its ability to intercalate DNA. was evaluated for bind DNA validate binding as the primary mechanism of cytotoxicity. Based on UV–vis absorbance titration data, K obs aaptamine 4.0 (±0.2) × 10 3 which essentially equivalent known intercalator N‐ [2‐(diethylamino)ethyl]‐9‐aminoacridine‐4‐carboxamide. Semi‐synthetic core modifications were performed improve general structural diversity analogs and vary absorption characteristics....
Carboxylesterases (CEs) are ubiquitous enzymes that responsible for the metabolism of xenobiotics, including drugs such as irinotecan and oseltamivir. Inhibition CEs significantly modulates efficacy agents. We report here β-lapachone is a potent, reversible CE inhibitor with Ki values in nanomolar range. A series amino phenoxy analogues have been synthesized, although former very poor inhibitors, latter compounds highly effective modulating activity. Our data demonstrate tautomerism...
Two new diterpene glycosides have been isolated from a commercial extract of the leaves Stevia rebaudiana. Compound 1 was shown to be 13-[(2-O-β-d-glucopyranosyl-3-O-β-d-glucopyranosyl-β-d-xylopyranosyl)oxy]ent-kaur-16-en-19-oic acid β-d-glucopyranosyl ester (rebaudioside R), while compound 2 determined 13-[(2-O-α-d-glucopyranosyl-β-d-glucopyranosyl)oxy]ent-kaur-16-en-19-oic 2-O-α-l-rhamnopyranosyl-β-d-glucopyranosyl S). Six additional known compounds were identified, dulcoside B,...
Several dibromotyramine derivatives including moloka'iamine were selected as potential zebra mussel (Dreissena polymorpha) antifoulants due to the noteworthy absence of fouling observed on sponges order Verongida. Sponges Verongida consistently produce these types bromotyrosine-derived secondary metabolites. Previously reported antifouling data for barnacle Balanus amphitrite(EC50 = 12.2 microM) support results here that compound may be a antifoulant (EC50 10.4 microM). The phytotoxic...
In order to expand the repertoire of antifungal compounds a novel, high-throughput phenotypic drug screen targeting fungal phosphatidylserine (PS) synthase (Cho1p) was developed based on antagonism toxin papuamide A (Pap-A). Pap-A is cyclic depsipeptide that binds PS in membrane wild-type Candida albicans, and permeabilizes its plasma membrane, ultimately causing cell death. Organisms with homozygous deletion CHO1 gene (cho1ΔΔ) do not produce are able survive presence Pap-A. Using this...
Amino- and urea-substituted thiazoles exhibited in vivo herbicidal activity on duckweed (Lemna paucicostata Hegelm. strain 6746) cultures appeared to act via inhibition of photosynthetic electron transport system. A small number the thiazole derivatives tested were active but only at relatively high concentrations. The most structures amino-substituted with isopropyl n-butyl side chains p-chlorophenyl chain. Decreasing length chain had a negative effect PSII inhibitory activity. series was...
The roots of Salvia miltiorrhiza ("Danshen") have been used in Chinese herbal medicine for centuries a host different conditions. While the exact nature active components this material are unknown, large amounts tanshinones present extracts derived from these samples. Recently, demonstrated to be potent human carboxylesterase (CE) inhibitors, with ability modulate biological activity esterified drugs. During course studies, we also identified more active, irreversible inhibitors enzymes. We...
With ∼ 40 years of research completed after the development self-contained underwater breathing apparatus, drug discovery opportunities in sea are still too numerous to count. Since FDA approval direct-from-the-sea calcium channel blocker ziconotide, marine natural products have been validated as a source for new medicines. However, demand is extremely high due high-throughput assays and this bottleneck has created need an intense focus on increasing rate isolating elucidating structures...
Histone lysine demethylases (KDMs) play critical roles in oncogenesis and therefore may be effective targets for anticancer therapy. Using a time-resolved fluorescence resonance energy transfer demethylation screen assay, combination with multiple orthogonal validation approaches, we identified geldanamycin its analog 17-DMAG as KDM inhibitors. In addition, found that these Hsp90 inhibitors increase degradation of the alveolar rhabdomyosarcoma (aRMS) driver oncoprotein PAX3-FOXO1 induce...
A novel cystine knot peptide, asteropsin E (ASPE), was isolated from an Asteropus sp. marine sponge. The primary, secondary, and tertiary structures of ASPE were determined by high-resolution 2D NMR spectroscopy (900 MHz). With the exception N-terminal modification, shares properties with previously reported asteropsins A-D, that is, absence basic residues, a highly acidic nature, conserved structurally important residues (including two cis-prolines), structural framework. found to be...
A diverse library of pre-fractionated plant extracts, generated by an automated high-throughput system, was tested using in vitro anti-malarial screening platform to identify known or new natural products for lead development. The identifies hits on the basis growth inhibition Plasmodium falciparum and counter-screens cytotoxicity human foreskin fibroblast embryonic kidney cell lines. physical supplemented early-stage collection analytical data each fraction aid rapid identification active...
Abstract Deep Gas exploration wells in the Fahud Salt Basin located North Oman were traditionally drilled with high mud weights. Due to this conventional drilling practice low permeability reservoirs and inherent petrophysical measurement sampling limitations, a level of uncertainty remained as presence producible (or commercial) gas. This resulted an increased risk when decision complete, hydraulically fracture production test was taken – or conversely, well abandoned. Often, even results...