Rocaglamides are bioactive natural compounds which have a cyclopenta[b]benzofuran core structure. The total synthesis of a reported natural product, 3'-hydroxymethylrocaglate (5), was achieved using [3 + 2] cycloaddition between 3-hydroxyflavone and methyl cinnamate. We also describe the synthesis of rocaglamide heterocycle derivatives and evaluate their Wnt signal inhibitory activities. Compounds 4, 5, 22a, 22b, 22c and 23c showed potent Wnt signal inhibitory activity.
In recent times, oncolytic viruses expressing an extraneous gene have attracted great interest; in fact, they have been engaged in multiple applications, such as medicine for cancer. Our group made an oncolytic adenovirus, namely, OBP-301, for use in treating solid cancers and press clinical trial to get approval for a pharmaceutical product. In this study, we applied a flow cytometry-based method to determine the titer of adenoviruses expressing an extraneous gene as well as assess their quality. We considered using the green fluorescent protein (GFP) 50 titer as a measure of viral quality. The GFP 50 titer (GFP 50 /mL) is the viral load required to render the HeLa S3 cell line 50% GFP-positive by analysing flow cytometry data. We measured the GFP 50 titers for three types of recombinant adenoviruses (OBP-401, OBP-1101, and OBP-1106). We compared GFP 50 /mL and tissue culture infectious dose (TCID 50 /mL), a conventional titration index, and found that these titers showed a linear correlation, with a correlation coefficient of >0.9. Moreover, GFP 50 /mL showed high repetitive accuracy. We expect this flow cytometry-based method to be useful in case of clinically relevant viruses expressing an extraneous gene, in particular, to control viral quality.
The hedgehog (Hh) signaling pathway performs important roles in embryonic development and cellular proliferation and differentiation. However, in many cancer cells Hh signaling is aberrantly activated, which has provided a strong impetus for the development of Hh pathway inhibitors. To address this, we synthesized a series of heterocyclic flavonoids and evaluated their Hh signaling inhibitory activity on cancer cell lines using our cell-based assay system. Of the synthetic flavonoids, compounds 4a and g showed good inhibitory activity (IC 50 was 16.8 and 21.8 µM, respectively), and were cytotoxic toward human pancreatic (PANC1) and prostate (DU145) cancer cells in which Hh signaling was activated. Compounds 4a and g had moderate selectivity against PANC1 cells. Western blotting analyses revealed that PTCH and GLI1 expression was reduced after treatment with these compounds. Overall, these synthetic flavonoids represent promising new additions to our expanding panel of Hh pathway inhibitors, and with further development these molecules may ultimately be considered for clinical use.
In the Minamata Bay, the remediation project on water and bottom sediment environment was completed in 1990. About 0.8 million m3 of bottom sediment contaminated by mercury was dredged. However, a recent measurement of mercury in the sediments [Tomiyasu et al.,2000] has shown that mercury is spreading around the center and southern parts of the Yatsushiro Sea from the Minamata Bay. Although the concentration of mercury in bottom sediment is lower nowadays (<10ppm), modelling for accurate prediction of mercury dynamics is necessary. In order to predict the mercury dynamics accurately in a coastal area, it is necessary to measure mercury transport in an actual sea. Thus, the current observation by using ADCP (RD Instruments Workhorse 1,200kHz), which was mounted on the side of a fishing boat, was performed on the 2nd of December, 2002 and the 29th of July, 2003 to realize a three-dimensional structure of tidal current in the Minamata Bay. As a result, it was found that a horizontal circulation flow occurred during ebb tide in summer.
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