Copper-obatoclax derivative complexes mediate DNA cleavage and exhibit anti-cancer effects in hepatocellular carcinoma.

Obatoclax is an indole-pyrrole compound that induces cancer cell apoptosis through targeting the anti-apoptotic Bcl-2 protein family. Previously, we developed a series of obatoclax derivatives and studied their STAT3 inhibition-dependent activity against cancer cell lines. The obatoclax analog, prodigiosin, has been reported to mediate DNA cleavage in cancer cells by coordinating with copper complexes. To gain an understanding of copper-obatoclax complex activity, we applied obatoclax derivatives to examine their copper-mediated nuclease activity as a means to establish a basis for structure activity relationship. Replacement of the indole ring of obatoclax with furanyl, thiophenyl or Boc-indolyl rings reduced the DNA cleavage ability. The same effect was achieved through the replacement of the obatoclax pyrrolyl ring with thiazolidinedione and thioacetal. Among the compounds tested, we demonstrated that the complex of obatoclax or compound 7 with copper exhibited potent DNA strand scission which correlated with HCC cell growth inhibition.

People's preference patterns for gains/losses in multiple time period situations.

Little research to date has been devoted to investigating whether people treat time differently from money when facing multiple gains or losses. This study tested the hypothesis that because time is characterized by perishability, fixed supply, and infungibility, people with strong motivation to obtain a long period of uninterrupted discretionary time would strive to trim the time needed for non-discretionary activities or to combine several non-discretionary activities. As a result, people prefer integration over segregation of multiple time losses or gains, which is not consistent with the prediction based on hedonic editing theory or the renewable resource model. This proposition is supported by results from four experiments.