Synthesis and biological evaluation of dialkylsubstituted maleic anhydrides as novel inhibitors of Cdc25 dual specificity phosphatases

Antiproliferative effect of natural tetrasulfides in human breast cancer cells is mediated through the inhibition of the cell division cycle 25 phosphatases

“…Then, cell pellets were thawed in 30 ml of lysis buffer [50 mM Tris-HCl pH 7.5, 250 mM NaCl, 1 mM EDTA, 0.1% Triton X-100, 0.1 mM PMSF, 3% (v/v) protease inhibitor cocktail (Sigma Chemical, USA)] and lysed by sonication (5x30 sec). After cell lysis, lysate was cleared by a 25,000 x g centrifugation for 45 min and fusion proteins were purified by affinity chromatography using glutathione-agarose gel as described (17).…”

Intermolecular Addition Reactions onto CC Multiple Bonds

“…In a recent application, Barton esters were found useful in the synthesis of natural and unnatural disubstituted maleimides or maleic anhydrides by way of two consecutive radical addition steps, as described in Scheme 3.27 [72].…”

Activity of novel Cdc25 inhibitors and preliminary evaluation of their potentiation of chemotherapeutic drugs in human breast cancer cells

“…This compound, as well as its derivatives, presents a hydrophilic substructure (γ-hydroxybutenolide residue) which serves as a surrogate phosphate whereas its hydrophobic substructure (long side chain) occupies a hydrophobic binding pocket when the molecule is bound to Cdc25A (Shimazawa et al, 2004). Based on this structural model, a series of 10 maleic anhydride derivatives 1a to 1j were synthesized in our laboratory and tested toward the three isoenzymes of human Cdc25 (Brault et al, 2007). Here, we investigated the cellular effect of 4 of these compounds selected for their variable in vitro Cdc25 inhibitory potentials.…”