A5031533425- Synthesis and Biological Evaluation
- Cellular transport and secretion
- Regulation of Appetite and Obesity
- S100 Proteins and Annexins
- Phenothiazines and Benzothiazines Synthesis and Activities
- Neuropeptides and Animal Physiology
- Synthesis and biological activity
- Click Chemistry and Applications
- Computational Drug Discovery Methods
- Sleep and Wakefulness Research
- Calcium signaling and nucleotide metabolism
- Cancer therapeutics and mechanisms
- Innovative Microfluidic and Catalytic Techniques Innovation
- Neonatal Respiratory Health Research
- Cancer, Hypoxia, and Metabolism
- Retinal Development and Disorders
- Bioactive Compounds and Antitumor Agents
- Neuroendocrine regulation and behavior
- Quinazolinone synthesis and applications
- Hypothalamic control of reproductive hormones
- HIV-related health complications and treatments
- HIV/AIDS drug development and treatment
- Analytical Chemistry and Chromatography
- Forensic Toxicology and Drug Analysis
- Pharmacological Effects and Toxicity Studies
University of Newcastle Australia
2016-2024
Newcastle University
2021
Callaghan Innovation
2016-2021
University of Tennessee at Knoxville
2018
Google (United States)
2018
Cancer Research UK
2011
Virginia Commonwealth University
2006-2009
Saint Louis University
2003-2005
Merck Canada Inc. (Canada)
2004
TransCanada (Canada)
2004
The effects of centrally injected orexin-A on plasma adrenocorticotropin (ACTH) and corticosterone levels corticotropin releasing factor (CRF) arginine vasopressin (AVP) mRNA in the parvocellular cells paraventricular nucleus (PVN) rat were investigated. In animals implanted previously with a lateral brain ventricle femoral artery cannula, single i.c.v. injection (10 microg/rat) resulted rapid, significant increase ACTH concentrations. Plasma reached peak (12.5-fold greater than basal...
This study examined drug interactions between buprenorphine, an opioid partial agonist medication used in the treatment of dependence, and nonnucleoside reverse-transcriptase inhibitors (NNRTIs) efavirenz (EFV) delavirdine (DLV). Opioid-dependent, buprenorphine/naloxone-maintained, human immunodeficiency virus (HIV)-negative volunteers (n=10 per NNRTI) participated 24-h sessions to determine pharmacokinetics buprenorphine with either EFV or DLV after administration standard doses...
Light-activable spatiotemporal control of PROTAC-induced protein degradation was achieved with novel arylazopyrazole photoswitchable PROTACs (AP-PROTACs). The use a promiscuous kinase inhibitor in the design enables this unique PROTAC to selectively degrade four kinases together on/off optical using different wavelengths light.
Abstract A simple, expedient continuously scalable flow chemistry synthesis of a range 1,4‐dimethylcarbazoles from substituted indoles and 2,5‐hexanedione in the presence K‐10 (montmorillonite clay) is reported. Optimization conditions led to development an in‐house K‐10/sand Omnifit TM catalyst column that at 140 °C 0.4 mL.min −1 afforded >90% conversion selected indole desired 1,4‐carbazole. This equates ca 80 mg.h production rate. The reaction was tolerant electron donating but not...
The endogenous, peptide ligand for the orphan receptors GPR7 and GPR8 was identified to be neuropeptide W (NPW). Because these are expressed in brain particular hypothalamus, we hypothesized that NPW might interact with neuroendocrine systems control hormone release from anterior pituitary gland. No significant effects of were observed on vitro releases prolactin (PRL), ACTH, or GH when log molar concentrations ranging 1 pM 100 nM incubated dispersed cells. However, NPW, injected into...
We examined drug interactions between buprenorphine, an opioid partial agonist available by prescription for treatment of dependence, and the protease inhibitors (PIs) nelfinavir (NFV), ritonavir (RTV), lopinavir/ritonavir (LPV/R). Opioid-dependent, buprenorphine/naloxone-maintained, human immunodeficiency virus (HIV)-negative volunteers (n=10 per PI) participated in 24-h pharmacokinetic studies, before after administration each PI. Symptoms opiate withdrawal excess were determined PI...
Background: Cardiac arrhythmias have been linked to treatment with methadone and levacetylmethadol. HIV-positive patients often conditions that place them at risk for QT interval prolongation including HIV–associated dilated cardiomyopathy, coronary artery disease as a consequence of highly active antiretroviral (ARV) therapy–associated metabolic syndrome, uncorrected electrolyte abnormalities. As February 14, 2006, no cases adverse events related reported in receiving buprenorphine, an...
Orexin is a hypothalamic neuropeptide that regulates feeding behavior in rats. Orexin-B has recently been cloned pigs and was shown to stimulate food intake after intramuscular injection. This study designed determine whether intracerebroventricular (ICV) intravenous injections of orexin could regulate appetite sheep. Suffolk wethers were moved indoor facilities, adapted diets for 6 wk, trained stand stanchions 3 h each day 2 wk before indwelling ICV cannulas installed. These sheep provided...
Abstract Neuropeptide B (NPB) was identified to be an endogenous, peptide ligand for the orphan receptors GPR7 and GPR8. Because is expressed in rat brain and, particular, hypothalamus, we hypothesized that NPB might interact with neuroendocrine systems control hormone release from anterior pituitary gland. No significant effects of were observed on vitro releases prolactin, adrenocorticotropic (ACTH) or growth (GH) when log molar concentrations ranging 1 p M 100 n incubated dispersed cells...
To improve outcomes among injection drug users with HIV and/or chronic hepatitis B, it is important to identify interactions between antiretroviral and opiate therapies. We report the results of a study designed examine interaction buprenorphine nucleos(t)ide reverse transcriptase inhibitors (NRTI) didanosine (ddI), lamivudine (3TC), tenofovir (TDF). Opioid-dependent, buprenorphine/naloxone-maintained, HIV-negative volunteers (n = 27) participated in two 24-hour sessions determine (1)...
Abstract Knoevenagel condensation of 3,4‐dichloro‐ and 2,6‐dichlorophenylacetonitriles gave a library dichlorophenylacrylonitriles. Our leads ( Z )‐2‐(3,4‐dichlorophenyl)‐3‐(1 H ‐pyrrol‐2‐yl)acrylonitrile 5 ) )‐2‐(3,4‐dichlorophenyl)‐3‐(4‐nitrophenyl)acrylonitrile 6 displayed 0.56±0.03 0.127±0.04 μ m growth inhibition (GI 50 260‐fold selectivity for the MCF‐7 breast cancer cell line. A 2,6‐dichlorophenyl moiety saw 10‐fold decrease in potency; additional nitrogen moieties (‐NO 2 enhanced...
Neuropeptide W (NPW) is produced in neurons located hypothalamus and brain stem, its receptors are present the hypothalamus, particular paraventricular nucleus (PVN). Intracerebroventricular (ICV) administration of NPW activated, a dose-related fashion, hypothalamic-pituitary-adrenal axis, as determined by plasma corticosterone levels conscious rats but, at those same doses, did not stimulate release oxytocin or vasopressin into peripheral circulation alter blood pressure heart rate. The...
S100a8 is a cytosolic protein expressed in myeloid cells where it forms stable heterodimer with another S100 family member, S100a9. The S100a9(-/-) mouse viable and phenotypically normal, whereas the S100a8(-/-) condition embryonic lethal. We present evidence that S100a8, without S100a9, has previously unrecognized role embryo development between fertilization 8-cell stage at day (E) 2.5. also second maternal deciduum, expression associated vasculature from E8.5 to formation of mature...
Multidrug-resistant (MDR) pathogens, particularly the ESKAPE group (Enterococcus faecalis/faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, and Enterobacter spp.), have become a public health threat worldwide. Development of new antimicrobial classes use drugs in combination are potential strategies to treat MDR pathogen infections promote optimal stewardship. Here, vitro activity robenidine analog NCL195 alone or with...
Protein covalent labeling can be an undesirable property of compounds being studied in drug discovery programs. Identifying such relies on the use radiolabeled material, which requires investment time and resources not typically expended until later process. We describe detection adducts to cytochrome P450 3A4, most abundant important from a human viewpoint, using liquid chromatography mass spectrometry. The technique is illustrated L-754,394 6',7'-dihydroxybergamottin, two known inhibitors...
The flow coupling of epichlorohydrin with substituted phenols, while efficient, limits the nature epoxide available for development focused libraries β-amino alcohols. This limitation was encountered in production analogues 1-(4-nitrophenoxy)-3-((2-((4-(trifluoromethyl)pyrimidin-2-yl)amino)ethyl)amino)propan-2-ol 1 , a potential antibiotic lead. situ (flow) generation dimethyldoxirane (DMDO) and subsequent olefin epoxidation abrogates this afforded facile access to structurally diverse...
Lead (Z)-N-(4-(2-cyano-2-(3,4-dichlorophenyl)vinyl)phenyl)acetamide, 1 showed MCF-7 GI50 =30 nM and 400-fold selective c.f. MCF10A (normal breast tissue). Acetamide moiety modification (13 a-g) to introduce additional hydrophobicity was favoured with cancer cell activity enhanced at 1.3 nM. Other analogues were potent against the HT29 colon line 23 Textbook SAR data observed in line, an MTT assay, via ortho (17 a), meta b) para f). The amino alcohol -OH pivotal, but no stereochemical...
Abstract To exploit the interaction of aryl hydrocarbon receptor (AhR) pathway in developing breast‐cancer‐specific cytotoxic compounds, we examined breast cancer selectivity and docking pose AhR ligands ( Z )‐2‐(2‐aminophenyl)‐1 H ‐benzo[ de ]isoquinoline‐1,3(2 )‐dione (NAP‐6; 5 ) 10‐chloro‐7 ]benzo[4,5]imidazo[2,1‐ a ]isoquinolin‐7‐one (10‐Cl‐BBQ; 6 ). While vitro is known, discuss SAR around this lead and, by using phenotypic cell‐line screening MTT assay, show for first time that also...