343256-43-9Relevant academic research and scientific papers
Epigenetic profiling of the antitumor natural product psammaplin A and its analogues
Garcia, Jose,Franci, Gianluigi,Pereira, Raquel,Benedetti, Rosaria,Nebbioso, Angela,Rodriguez-Barrios, Fatima,Gronemeyer, Hinrich,Altucci, Lucia,Lera, Angel R. De
, p. 3637 - 3649 (2011/08/03)
A collection of analogues of the dimeric natural product psammaplin A that differ in the substitution on the (halo)tyrosine aryl ring, the oxime and the diamine connection has been synthesized. The effects on cell cycle, induction of differentiation and apoptosis of the natural-product inspired series were measured on the human leukaemia U937 cell line. Epigenetic profiling included induction of p21WAF1, effects on global H3 histone and tubulin acetylation levels as well as in vitro enzymatic assays using HDAC1, DNMT1, DNMT3A, SIRT1 and a peptide domain with p300/CBP HAT activity. Whereas the derivatives of psammaplin A with modifications in the length of the connecting chain, the oxime bond and the disulfide unit showed lower potency, the analogues with changes on the bromotyrosine ring exhibited activities comparable to those of the parent compound in the inhibition of HDAC1 and in the induction of apoptosis. The lack of HDAC1 activity of analogues modified on the disulfide bond suggests that its cleavage must occur in cells to produce the monomeric Zn2+-chelating thiol. This assumption is consistent with the molecular modelling of the complex of psammaplin A thiol with h-HDAC8. Only a weak inhibition of DNMT1, DNMT3A and residual activities with SIRT1 and a p300/CBP HAT peptide were measured for these compounds.
Approaches to the synthesis of some tyrosine-derived marine sponge metabolites: Synthesis of verongamine and purealidin N
Boehlow,Harburn,Spilling
, p. 3111 - 3118 (2007/10/03)
The oxidation of tyrosine ethyl ester (7) with Na2WO4/H2O2 in ethanol, dimethyldioxirane in acetone, or methyltrioxorhenium/H2O2 in EtOH gave the corresponding tyrosine oxime (8) in high yi
