| The synthesis and reductive alkylation studies of purine-like imidazo (4,5-g) -quinazoline-4,9-dione analogues were carried out in conjunction with the design of purine-active-site-directed reductive alkylators. The design involved functionalization of the purine-like imidazo (4,5-g) -quinazoline ring system as a quinone (4,9-dione) bearing a 2;Hydrolysis studies showed that hypoxanthine-like imidazo (4,5-g) quinazolin-4,9-diones bearing a 2-;Also, it was observed that the hydroquinone form, like quinone derivatives, can enter the active site of xanthine oxidase. Thus, the observed alkylation of the enzyme by these derivatives may thus pertain to quinone methide generation and nucleophilic trapping during enzymatic oxidation at 6-position of substrate.;Enzymatic studies also indicate that imidazo (4,5-g) quinazoline-4,9-dione system can oxidize the enzyme. Thus, the reduced enzyme transfers electrons to the quinone and resulting hydroquinone can then inactivate the enzymes. As with mitomycin C, reduction and quinone methide formation is essential for alkylation by the titled quinones. Therefore, this imidazo (4,5-g) quinazolin-4,9-dione system is an example of a purine-active-site-directed reductive alkylator.;Xanthine oxidase mediated oxidation of the hypoxanthine-like imidazo (4,5-g) quinazolin-4,9-dione indicate that these derivatives are excellent purine mimics. The catalytic parameters are comparable to the natural substrate in spite of the 2.4 A;Also, the bisalkylating imidazo (4,5-g) quinazoline-4,9-dione reductive alkylators bearing leaving groups in the 2-... |
