Discovery of a Novel Template, 7-Substituted 7-Deaza-4'-Thioadenosine Derivatives as Multi-Kinase Inhibitors.

The development of anticancer drugs remains challenging owing to the potential for drug resistance. The simultaneous inhibition of multiple targets involved in cancer could overcome resistance, and these agents would exhibit higher potency than single-target inhibitors. Protein kinases represent a promising target for the development of anticancer agents. As most multi-kinase inhibitors are heterocycles occupying only the hinge and hydrophobic region in the ATP binding site, we aimed to design multi-kinase inhibitors that would occupy the ribose pocket, along with the hinge and hydrophobic region, based on ATP-kinase interactions. Herein, we report the discovery of a novel 4'-thionucleoside template as a multi-kinase inhibitor with potent anticancer activity. The in vitro evaluation revealed a lead 1g (7-acetylene-7-deaza-4'-thioadenosine) with potent anticancer activity, and marked inhibition of TRKA, CK1δ, and DYRK1A/1B kinases in the kinome scan assay. We believe that these findings will pave the way for developing anticancer drugs.

Oxidation resistance of iron and copper foils coated with reduced graphene oxide multilayers.

Protecting the surface of metals such as Fe and Cu from oxidizing is of great importance due to their widespread use. Here, oxidation resistance of Fe and Cu foils was achieved by coating them with reduced graphene oxide (rG-O) sheets. The rG-O-coated Fe and Cu foils were prepared by transferring rG-O multilayers from a SiO(2) substrate onto them. The oxidation resistance of these rG-O-coated metal foils was investigated by Raman spectroscopy, optical microscopy, and scanning electron microscopy after heat treatment at 200 °C in air for 2 h. The bare metal surfaces were severely oxidized, but the rG-O-coated metal surfaces were protected from oxidation. This simple solution process using rG-O is one advantage of the present study.