Development of small molecule inhibitors of the histone acetyltransferase p300/CBP associated factor (PCAF) is relevant for oncology. The inhibition of the enzyme PCAF and proliferation of the cancer cell line HEP G2 by a series of 5-chloroisothiazolones was compared to a series of 5-chloroisothiazolone-1-oxides. The PCAF inhibitory potency of 5-chloroisothiazolones and 5-chloroisothiazolone-1-oxides is influenced by substitution in the 4-position. A study on the reactivity of the HAT inhibitors towards thiols and thiolates indicates that 5-chloroisothiazolones reacted quickly with propane-1-thiolate to provide many products, whereas 5-chloroisothiazolone-1-oxides provide only one defined product. Growth inhibition studies indicate that 5-chloroisothiazolones inhibit proliferation of HEP G2 cells at concentrations between 8.6 and 24 microM, whereas 5-chloroisothiazolone-1-oxides required higher concentrations or showed no inhibition.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejmech.2009.07.025 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The important role of the histone acetyltransferases p300/CBP in cancer and the promising anticancer effects of p300/CBP inhibitors.
Cell Biol Toxicol
January 2025
Department of Ultrasound, Shengjing Hospital of China Medical University, 110004, Shenyang, Liaoning, China.
Histone acetyltransferases p300 (E1A-associated protein p300) and CBP (CREB binding protein), collectively known as p300/CBP due to shared sequence and functional synergy, catalyze histone H3K27 acetylation and consequently induce gene transcription. p300/CBP over-expression or over-activity activates the transcription of oncogenes, leading to cancer cell growth, resistance to apoptosis, tumor initiation and development. The discovery of small molecule inhibitors targeting p300/CBP histone acetyltransferase activity, bromodomains, dual inhibitors of p300/CBP and BRD4 bromodomains, as well as proteolysis-targeted-chimaera p300/CBP protein degraders, marks significant progress in cancer therapeutics.
View Article and Find Full Text PDFHistone Deacetylation in Alzheimer's Diseases (AD); Hope or Hype.
Cell Biochem Biophys
January 2025
Department of Medical Laboratories Technology, AL-Nisour University College, Baghdad, Iraq.
Histone acetylation is the process by which histone acetyltransferases (HATs) add an acetyl group to the N-terminal lysine residues of histones, resulting in a more open chromatin structure. Histone acetylation tends to increase gene expression more than methylation does. In the central nervous system (CNS), histone acetylation is essential for controlling the expression of genes linked to cognition and learning.
View Article and Find Full Text PDFCurcumin pretreatment prevents butyrate-induced cell death and release of damage-associated molecular patterns on gingival epithelial Ca9-22 cells.
J Oral Biosci
January 2025
Department of Biochemistry, Nihon University School of Dentistry, Tokyo, Japan; Division of Functional Morphology, Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan. Electronic address:
Objectives: Exposure of gingival epithelial cells to butyrate, a short-chain fatty acid produced by dental plaque bacteria, cause cell death and subsequent damage-associated molecular pattern (DAMP) release. We investigated the effects of curcumin, a polyphenol extracted from turmeric, on butyrate-induced human gingival epithelial Ca9-22 cell death and DAMP release.
Methods: Ca9-22 cells were pretreated with curcumin before butyrate exposure.
Loss of Kat2b impairs intraflagellar transport and the Hedgehog signaling pathway in primary cilia.
Sci Rep
January 2025
Department of Biological Science, Sookmyung Women's University, Seoul, 04310, Republic of Korea.
Primary cilia are sensory organelles that regulate various signaling pathways. When microtubules are compared to a highway, motor proteins carry and transport cargo proteins, which are tuned by post-translational modifications, such as acetylation. However, the role of acetylation in primary cilia regulation remains unclear.
View Article and Find Full Text PDFTubulin Acetylation Enhances Microtubule Stability in Trabecular Meshwork Cells Under Mechanical Stress.
Invest Ophthalmol Vis Sci
January 2025
Department of Ophthalmology, Duke Eye Center, Duke University, Durham, North Carolina, United States.
Purpose: To study the roles of tubulin acetylation and cyclic mechanical stretch (CMS) in trabecular meshwork (TM) cells and their impact on outflow pathway physiology and pathology.
Methods: Primary TM cell cultures were subjected to CMS (8% elongation, 24 hours), and acetylated α-tubulin at lysine 40 (Ac-TUBA4) was assessed by western blotting and immunofluorescence. Enzymes regulating tubulin acetylation were identified via siRNA-mediated knockdowns of ATAT1, HDAC6, and SIRT2.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!