A5036595564- Fluorine in Organic Chemistry
- Neuroblastoma Research and Treatments
- Histone Deacetylase Inhibitors Research
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Catalytic C–H Functionalization Methods
- Protein Degradation and Inhibitors
- Sulfur-Based Synthesis Techniques
- Ubiquitin and proteasome pathways
- Inorganic Fluorides and Related Compounds
- Cancer Treatment and Pharmacology
- Crystallography and molecular interactions
- Glioma Diagnosis and Treatment
- Chemical Synthesis and Analysis
- Antimicrobial agents and applications
- HER2/EGFR in Cancer Research
- Synthesis and bioactivity of alkaloids
- Phenothiazines and Benzothiazines Synthesis and Activities
- Asymmetric Synthesis and Catalysis
- Chemical synthesis and alkaloids
- Colorectal Cancer Treatments and Studies
- Chemical Synthesis and Reactions
- Antimicrobial Peptides and Activities
Children's Cancer Institute Australia
2020-2025
UNSW Sydney
2020-2023
The University of Sydney
2022
Cancer Institute of New South Wales
2021
Nanyang Technological University
2016
Albany Molecular Research (Singapore)
2014-2016
Herein we report a series of telescoping methodologies for one pot synthesis biologically relevant γ-carboline derivatives 6 and spiro[pyrrolidinone-3,3′]indole 7. Initially the three consecutive steps cyclopropanation, phthalimide deprotection, Boc-deprotection have been congregated in single reaction vessel to afford ∼1:1 mixture Next, careful optimization sequence conditions generated an orthogonal approach access compounds 7 exclusively. Air oxidation γ-carbolinones afforded aromatic...
Abstract Background: Deregulated expression of MYC family transcription factors is present in more than 70% human cancers. an intrinsically disordered protein without known drug binding pockets and essential for adult cell replication, making clinical development inhibitors challenging. MYCN amplification overexpression generate driver signals the childhood cancers, neuroblastoma (NB), medulloblastoma (MB) diffuse intrinsic pontine glioma (DIPG). Methods Results: We previously reported a...
Abstract Neuroblastoma is the most common extracranial solid tumor in children worldwide. We have found that high expression of RNAMT1 gene tissues associated with poor prognosis both MYCN-amplified [Overall survival (OS): p = 0.0409 and event-free (EFS): 0.0061] MYCN non-amplified neuroblastoma patients (OS: < 0.0001 EFS: 0.0001). Multivariable Cox regression analysis for patient [OS: hazard ratio (HR) 1.92, 0.003 HR 1.72, 0.0001] independent from current prognostic markers:...
Histone deacetylase (HDAC) inhibitors are effective in MYCN-driven cancers, because of a unique need for HDAC recruitment by the MYCN oncogenic signal. However, much more combination with other anti-cancer agents. To identify novel compounds which act synergistically inhibitor, such as suberanoyl hydroxamic acid (SAHA), we performed cell-based, high-throughput drug screen 10,560 small molecule from drug-like diversity library and identified compound (SE486-11) enhanced cytotoxic effects...
There has been an increasing interest in the development of antimicrobial peptides (AMPs) and their synthetic mimics as a novel class antibiotics to overcome rapid emergence antibiotic resistance. Recently, phenylglyoxamide-based small molecular AMP have identified potential leads treat bacterial infections. In this study, new series biphenylglyoxamide-based were synthesised from ring-opening reaction N-sulfonylisatin bearing biphenyl backbone with diamine, followed by conversion into...
Abstract Background: Medulloblastoma (MB) is the most prevalent malignant childhood brain tumour. Although prognosis has improved over time, 95% of children with high-risk or relapsed MB eventually succumb to disease. A key driver gene in c-MYC oncogene, for which there are currently no approved inhibitors. Histone deacetylases (HDACs) transcriptional repressors that dysregulated many cancers, making them an attractive therapeutic target. several HDAC inhibitors have been FDA-approved cancer...
A facile procedure for the copper-mediated oxidative trifluoromethylthiolation of potassium aryl- and heteroaryltrifluoroborates with Ruppert–Prakash reagent elemental sulfur is presented. Aryl trifluoromethyl thioethers can be prepared in good to moderate yield under mild reaction conditions.
The synthesis of fluorinated arenes by the iron-mediated fluorination potassium aryltrifluoroborates with Selectfluor<sup>®</sup> and fluoride is described. fluorination reaction uses commercially available reagents without requiring addition exogenous ligands. Fluorinated compounds were obtained in moderate to good yields under mild conditions.
Abstract This modified, robust and simple protocol for the fluorination of potassium aryl trifluoroborates furnishes fluorides a broad substrate scope in good yields.
MYCN is a major oncogenic driver for neuroblastoma tumorigenesis, yet there are no direct inhibitors. We have previously identified PA2G4 as protein-binding partner of and drive tumorigenesis. A small molecule known to bind PA2G4, WS6, significantly decreased tumorigenicity in TH-MYCN mice, along with the inhibition interactions. Here, we number novel WS6 analogues, 80% structural similarity, used surface plasmon resonance assays determine their binding affinity. Analogues #5333 #5338 showed...
The reactivity and synthesis of new analogues pyrido[1,2-a]benzimidazoles have been explored. Twenty-three derivatives bearing phenoxy, thiophenoxy, aniline, aryl groups at the 1-position were successfully synthesised in 25–91% yield, via nucleophilic substitution, Buchwald–Hartwig amination, Suzuki coupling type processes. Solvent free synthetic protocols employed to achieve substitution anilines with electron donating or moderately withdrawing on a sterically demanding intermediate (7a)....
The MYCN oncogene and histone deacetylases (HDACs) are key driver genes in the childhood cancer, neuroblastoma. We recently described a novel pyridobenzimidazole analogue, SE486-11, which enhanced therapeutic effectiveness of HDAC inhibitors by increasing ubiquitination through effects on deubiquitinase, ubiquitin-specific protease 5 (USP5). Here we describe synthesis series pyrimido[1,2-a]benzimidazole derivatives, an evaluation their cytopathic against non-malignant human neuroblastoma...