The discovery of novel 5,7-disubstituted[1,6]naphthyridines as potent inhibitors of Spleen Tyrosine Kinase (SYK) is discussed. The SAR reveals the necessity for a 7-aryl group with preference towards para substitution and that this in combination with 5-aminoalkylamino substituents further improved the potency of the compounds. The initial SAR as well as a survey of the other positions is discussed in detail.
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http://dx.doi.org/10.1016/s0960-894x(03)00163-x | DOI Listing |
Sci Rep
January 2025
Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
In this study, new cinnamic acid linked to triazole acetamide derivatives was synthesized and evaluated for anti-Alzheimer and anti-melanogenesis activities. The structural elucidation of all analogs was performed using different analytical techniques, including H-NMR, C-NMR, mass spectrometry, and IR spectroscopy. The synthesized compounds were assessed in vitro for their inhibitory activities against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and tyrosinase enzymes.
View Article and Find Full Text PDFMol Cell
January 2025
Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia; Department of Haematology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Centre for Cancer Research, University of Melbourne, Melbourne, VIC, Australia. Electronic address:
Several transcription inhibitors have been developed as cancer therapies. However, they show modest clinical activity, highlighting that our understanding of the cellular response to transcriptional inhibition remains incomplete. Here we report that potent inhibitors of transcription not only impact mRNA output but also markedly impair mRNA transcript localization and nuclear export.
View Article and Find Full Text PDFBioorg Chem
December 2024
Good Clinical Practice Development, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China. Electronic address:
Inhibition of human concentrative nucleoside transporter 2 (CNT2) could suppress increases in serum urate levels derived from dietary purines. However, the structural basis for substrate recognition of CNT2 is still unknown and only a few inhibitors have been reported. In this study, a homology model of CNT2 was constructed and residues T315, E316, N426, N491, E492, F536 and N538 were identified as binding sites for adenosine through site-directed mutagenesis and a H-adenosine uptake assay.
View Article and Find Full Text PDFPhytomedicine
December 2024
Scabies Laboratory, Infection and Inflammation Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; School of Biomedical Sciences, University of Queensland, St Lucia, Brisbane, QLD, Australia. Electronic address:
Background: Scabies is a debilitating and neglected infectious disease with limited effective treatment options and affecting millions of people worldwide, mainly in poor and overcrowded settings. Essential oils from Australasian Myrtaceae are known to have parasiticidal properties, often attributed to the presence of β-triketones, which are known inhibitors of the tyrosine catabolism pathway through inhibition of hydroxyphenylpyruvate dioxygenase (HPPD).
Purpose: In this study, essential oils from mānuka (Leptospermum scoparium) were evaluated in vitro for miticidal and ovicidal activities and their active β-triketone constituents (flavesone, leptospermone, and isoleptospermone) were identified.
PLoS One
January 2025
Center of Medical and Bio-Allied Health Sciences Research (CMBHSR), Ajman University, Ajman, United Arab Emirates.
Epigenetic processes are the critical events in carcinogenesis. Histone modification plays a crucial role in gene expression regulation, where histone deacetylases (HDACs) are key players in epigenetic processes. Inhibiting HDACs has shown promise in modern cancer therapy.
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