Drug-Induced Blood Breakdown Probed | Chemical & Engineering News
Volume 91 Issue 44 | p. 29 | Concentrates
Issue Date: November 4, 2013

Drug-Induced Blood Breakdown Probed

Details of breakdown process reveal route to rational design of less toxic agents
Department: Science & Technology
News Channels: Biological SCENE, Organic SCENE
Keywords: drug design, hemoglobin, blood, nitroso

Some amine- and nitro-containing drugs degrade human blood by destroying hemoglobin, causing anemia and other problems. The drugs could be redesigned to minimize or prevent such side effects, but the molecular-level understanding of the destruction process needed to aid redesign has not been available. Jun Yi, George B. Richter-Addo, and coworkers at the University of Oklahoma have now nailed down key details of the process (Chem. Commun., DOI: 10.1039/c3cc46174b). The drugs, such as the urinary tract analgesic phenazopyridine, are known to convert in the body to alkyl- or aryl-nitroso metabolites that bind hemoglobin. In the new study, the researchers trapped the key hemoglobin-degradation intermediates generated by alkyl-nitroso metabolites and determined their structures. The work reveals that methyl-nitroso derivatives do not cause degradation, but ethyl-nitroso metabolites do. The finding could aid the rational design of modified drugs that avoid ethyl-nitroso formation and thus cause less toxicity from hemoglobin breakdown.

 
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