Abstract
In this thesis, I reported a synthetic route for the preparation of benzimidazole derivatives as new anti-hepatitis C virus agents. Furthermore, I also explored the DNA cleaving ability and antitumor activity of novel binuclear-platinum complexes, which can perform single-strand scission upon UV irradiation. In part I of this thesis, totally 39 new conjugated compounds were successfully synthesized by a one-flask method from benzimidazole or it relative analogs including imidazopyridine, purine, benzoxazole, and benzothiazole with coumarin derivatives. In part I of section A, a methylthio linker was used to connect these two classes of compounds, onto which were attached with various substituents for establishment of the structure–activity relationship. Structural–activity relationships from the HCV inhibition activity indicated the –CH2–coumarin moiety with purine nuclei was essential for the enhancement of selectivity. In part I of section B, a new compound library was established, which contained 20 hinged benzimidazole–coumarin hybrids and their □-D-furanosides. Structure–activity relationship of these conjugated compounds is illustrated on the basis of the functional groups attached onto the nuclei of benzimidazole, coumarin, and furanose. In Part II of this thesis, a series of novel binuclear-platinum complexes were synthesized by adding sodium 2-mercaptopyridine N-oxide and sulfoxide with poly(ethylene glycol) (PEG) as a linker to K2PtCl4 in DMF. In vitro growth inhibitory effect of those organoplatinum complexes were evaluated in human cancer cell lines HeLa and OECM-1. The result showed that these new binuclear-platinum complexes exhibited remarkably anticancer activity.