Abstract
In this thesis, I developed a synthetic route for the preparation of phthalimide derivatives as novel photo-induced DNA cross-linking agents. I also explored the DNA cleaving ability of oxime esters, which can perform double-strand scission upon UV irradiation. Furthermore, a series of benzimidazoles were prepared and screened their inhibitions against HCV. In part 1 of this thesis, three new photo-induced DNA cross-linking agents were synthesized. Irradiation with UV light (312 nm) of these cross-linking agents in a phosphate buffer containing the linearized pBR322 DNA afforded the DNA cross-links. In part 2, a compound library containing 63 O-benzoyl oxime esters was set up from condensation of meta- or para-substituted benzoyl, 1-naphthoyl or 2-naphthoyl chlorides with oximes of seven different kinds of intercalators. Irradiation with UV light (312 nm) of these oxime esters containing the supercoiled circular φX174 RFI DNA under aerobic conditions for 2.0 h resulted in the single-strand scission of DNA. Results from control experiments indicate that UV light functioned as a "trigger" to initiate the DNA cleavage processes. In part 3, totally 24 new conjugated compounds were successfully synthesized by a one-flask method from benzimidazole and courmarine derivatives. 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–coumarine moiety with Br substituent at the C-6’ position was essential for the enhancement of selectivity.