The phytochemical piceatannol induces the loss of CBL and CBL-associated proteins.

Piceatannol is a naturally occurring bioactive stilbene with documented antileukemic properties. It has been extensively used as a Syk-selective protein tyrosine kinase inhibitor for the study of various signaling pathways. Herein, we show that the hydroxystilbene, piceatannol, and related catechol ring-containing compounds are able to induce the loss of the Cbl family of proteins. Normal cellular Cbl-regulatory mechanisms were not involved in this process. Screening of a small library of piceatannol-like compounds indicated that aromaticity and a catechol ring were required for the induction of Cbl loss. Further examination of these two chemical properties showed that the oxidative conversion of the catechol ring of piceatannol into a highly reactive O-benzoquinone was the cause of piceatannol-induced Cbl loss. Characterization of the Cbl selectivity of piceatannol-induced protein loss revealed that this compound was also able to induce the functional loss of specific Cbl-associated proteins involved in signaling pathways commonly associated with cancer. This work uncovers a new, piceatannol-dependent effect and shows a novel way in which this phenomenon can be exploited to inhibit disease-associated signaling pathways.

Derivatives of substituted 3-trichlorogermylpropionic acid.

The central Ge atoms in the structures of 3-(2-fluorophenyl)-3-(triphenylgermyl)propionic acid, [Ge(C(6)H(5))(3)(C(9)H(8)FO(2))], 3-(2-tolyl)-3-(tri-4-tolylgermyl)propionic acid, [Ge(C(7)H(7))(3)(C(10)H(11)O(2))], and 3-(4-tolyl)-3-(tribenzylgermyl)propionic acid, [Ge(C(7)H(7))(3)(C(10)H(11)O(2))], are four-coordinate with slightly distorted tetrahedral geometry. The Ge-Csp(3) distances [1.970 (3)-1.997 (3) A] are significantly longer than the Ge-C(aromatic) distances [1.940 (3)-1.959 (2) A]. In all three structures, the molecules form dimeric pairs about inversion centres through strong hydrogen-bonding interactions between carboxylic acid groups.