Biologically Active Conjugates of Drugs and Toxic Chemicals

摘要: Conjugation reactions associated with metabolism of drugs and xenobiotics function primarily as detoxification pathways (Caldwell 1982); however, they also serve to convert drug metabolites either compounds that are biologically active per se or prodrugs carriers biological activity various tissues. This chapter reviews important examples the role phase II in generating compounds. Among earliest this phenomenon is formation potent carcinogenic by conjugation. In late 1960s, Millers their colleagues found sulfation N-hydroxy-N-2-fluorenylaeetamine generated a reactive electrophile caused cancer rodents (Miller et al. 1974). similar findings glucuronide (Irving 1971; Maher Reuter 1973) led concept metabolic activation required for generation wide range carcinogens toxic chemicals. Newer aspects conjugation toxicity carcinogenesis reviewed Chaps. 14, 15, 16 volume. Phase directly activate forms enhance availability extrahepatic tissues described below. Some conjugates produced liver transported target must be hydroloyzed require further