No abstract

No abstract

No abstract

No abstract

As important cell cycle regulators, Cdc25s are key Cdk activating proteins and act by dephosphorylation of conserved Cdk residues. Since Cdc25 protein was first found as the twenty-fifth protein to be related to the cell division cycle, 1 three different members, Cdc25A,-B, and-C were identified in humans 2 and several splice variants of Cdc25 proteins have also been reported. 3 The evidence that Cdc25A and-B are overexpressed and likely important for the growth of different types of human cancer, 4 has stimulated the search for Cdc25 inhibitors. However the literature on Cdc25 inhibition is in its infancy and inhibitor design strategies are just now emerging. 5 Recently, several 1,4-naphthoquinones have proven to be effective at inhibiting Cdc25, including vitamin K 3. 6 Among them, vitamin K derivative, Cpd 5 (2-(2-mercaptoethanol)-3methyl-1,4-naphthoquinone) was found to be one of the most growth inhibitors in vitro of various tumor cell lines in the range of 9-30 µM, 6c and markedly less active against PTP1B and other dual specificity phoaphatases, VHR and MKP-1. 7 Previously, we also demonstrated that the 1,4naphthoquinone derivatives with the hydroxy group at C-5 and/or C-8 of the benzene ring was more active than vitamin K 3 on Cdc25A inhibition. 6b Therefore, in the current study, we synthesized mono-and dihydroxylated Cpd 5 derivatives 2 and 3 by addition of β-mercaptoethanol to the commercially available naphthoquinones in methanol. To examine the effects of these compounds on the growth of Hep3B cells in vitro, cells were cultured with several concentrations of Cpd 5 or hydroxylated Cpd 5 derivatives and a growth curve was drawn from the DNA amounts of each cell sample.