78659-97-9Relevant academic research and scientific papers
Comparative Toxicities and Analgesic Activities of Three Monomethylated Analogues of Acetaminophen
Harvison, Peter J.,Forte, Anthony J.,Nelson, Sidney D.
, p. 1737 - 1743 (1986)
Three monomethylated derivatives of 4'-hydroxyacetanilide (acetaminophen) were prepared in order to compare their cytotoxic potential and analgesic activity with that of acetaminophen.Only 4'-hydroxy-methylacetanilide (N-methylacetaminophen) was devoid of cytotoxic effects to hepatic tissue of mice.Results of comparative tissue distribution studies and metabolism studies both in vivo and in vitro in mice indicate that the disposition of N-methylacetaminophen is similar to that of acetaminophen except that it is not oxidized to a toxic metabolite.In contrast, 3'-methyl-4'-hydroxyacetanilide (3-methlacetaminophen) is as hepatotoxic as acetaminophen in mice while 2'-methyl-4'-hydroxyacetanilide (2-methylacetaminophen) is less hepatotoxic.The analgesic potency of the analogues seems to parallel their hepatotoxic potential, and both activities parallel the oxidation potentials in this series of compounds.
A small molecule binding to the coactivator CREB-binding protein blocks apoptosis in cardiomyocytes
Borah, Jagat C.,Mujtaba, Shiraz,Karakikes, Ioannis,Zeng, Lei,Muller, Michaela,Patel, Jigneshkumar,Moshkina, Natasha,Morohashi, Keita,Zhang, Weijia,Gerona-Navarro, Guillermo,Hajjar, Roger J.,Zhou, Ming-Ming
body text, p. 531 - 541 (2011/11/05)
As a master transcription factor in cellular responses to external stress, tumor suppressor p53 is tightly regulated. Excessive p53 activity during myocardial ischemia causes irreversible cellular injury and cardiomyocyte death. p53 activation is dependent on lysine acetylation by the lysine acetyltransferase and transcriptional coactivator CREB-binding protein (CBP) and on acetylation-directed CBP recruitment for p53 target gene expression. Here, we report a small molecule ischemin, developed with a structure-guided approach to inhibit the acetyl-lysine binding activity of the bromodomain of CBP. We show that ischemin alters post-translational modifications on p53 and histones, inhibits p53 interaction with CBP and transcriptional activity in cells, and prevents apoptosis in ischemic cardiomyocytes. Our study suggests small molecule modulation of acetylation-mediated interactions in gene transcription as a new approach to therapeutic interventions of human disorders such as myocardial ischemia.
