1025903-94-9Relevant academic research and scientific papers
Synthesis and biological testing of novel pyridoisothiazolones as histone acetyltransferase inhibitors
Furdas, Silviya D.,Shekfeh, Suhaib,Bissinger, Elisabeth-Maria,Wagner, Julia M.,Schlimme, Sonja,Valkov, Vassil,Hendzel, Michael,Jung, Manfred,Sippl, Wolfgang
experimental part, p. 3678 - 3689 (2011/08/03)
We present a combination of database screening, synthesis and in vitro testing to identify novel histone acetyltransferase (HAT) inhibitors. The National Cancer Institute compound collection (NCI) and several commercial databases were filtered by similarity-based virtual screening to find new HAT inhibitors. Employing the recombinant HAT p300/CBP-associated factor (PCAF) and two different histone substrates for screening, pyridoisothiazolones were identified as inhibitors of human PCAF. Due to the limited solubility of the initial hits, we synthesized and tested them on PCAF. The compounds inhibit the proliferation of cancer cells. In summary, valuable chemical tools and potential lead candidates for new anticancer agents directed against HATs as new targets have been identified.
Heteroaryl-Fused 2-Phenylisothiazolone Inhibitors of Cartilage Breakdown
Wright, Stephen W.,Petraitis, Joseph J.,Abelman, Matthew M.,Batt, Douglas G.,Bostrom, Lori L.,et al.
, p. 3071 - 3078 (2007/10/02)
The synthesis, biological evaluation, and structure-activity relationships of a series of N-phenyl heteroaryl-fused isothiazolones are described.These isothiazolones have been shown to exhibit potent, dose-dependent inhibition of IL-1β-induced breakdown of proteoglycan in a cartilage organ culture assay.This effect is likely due to inhibition of MMP activation and a consequent reduction in MMP activity following IL-1β stimulation.Thus these compounds potentially represent simple, non-peptidic disease-modifying agents for the treatment of arthritic diseases.To examine the effects of structure on in vitro activity, three general features of the molecules were varied, substituents on the pendant N-phenyl group, the position of ring fusion to the isothiazolone, and substituents on the fused ring peri to the isothiazolone sulfur.
