This thesis describes the preparation of several novel guanidine derivatives (where X=tetramethyl, dipiperidine and dimorpholine ); three containing a previously described trimethyl-substituted quinone I and three analogous guanidines containing the novel phenyl-substituted quinone II. These conformationally locked derivatives were tested as substrates in a benzoquinone-based drug delivery system which is activated by the enzyme
human quinone-oxidoreductase 1 (hNQOl). Molecular modelling studies were initially performed and demonstrated that all six derivatives were viable substrates of the enzyme hNQOl, as determined by the drug/hNQOl interactions. Following their successful preparation, these derivatives were subsequently analysed by high performance liquid chromatography (HPLC). Preliminary findings confirmed their ability to act as substrates for the enzyme hNQOl and showed they followed the intended mechanistic pathway for this drug delivery system. These results also indicated that the rate of reaction with hNQOl was faster for quinone I versus II and the reaction of II did not proceed to
completion.