Synthesis, hydrolytic reactivity, and anticancer evaluation of N- and O-triorganosilylated compounds as new types of potential prodrugs.
N- and O-Triorganosilylated compounds related to various anticancer agents were synthesized for evaluation as potential anticancer prodrugs. 1H-NMR and UV kinetic measurements of hydrolytic desilylation were used to correlate relative rates of structural unmasking with steric bulk about the silicon reaction center. The tert-butyldimethylsilyl ester of chlorambucil and a number of O- triorganosilylated carbamate derivatives of nor-nitrogen mustard showed significant activity against P-388 lymphocytic leukemia in mice.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D006868:Hydrolysis; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D009588:Nitrogen Mustard Compounds / Q000138:chemical synthesis* / Q000627:therapeutic use; D013056:Spectrophotometry, Ultraviolet
D000970:Antineoplastic Agents; D009588:Nitrogen Mustard Compounds