How can chirality and stereoisomers influence the pharmacology, bioactivity, toxicology, pharmacokinetics, and metabolism of ibuprofen? Please provide a detailed summary of what might happen if, for instance, the R enantiomer isn't able to be inverted to the bioactive S enantiomer.
How can chirality and stereoisomers influence the pharmacology, bioactivity, toxicology, pharmacokinetics, and
Please provide a detailed summary of what might happen if, for instance, the R enantiomer isn't able to be inverted to the bioactive S enantiomer.
Ibuprofen is a Non-Steroidal Anti-Inflammatory Drug (NSAID). Ibuprofen does this function by inhibiting a cyclooxygenase (COX) enzyme called Prostaglandin H2 synthase. This enzyme have cyclooxygenase and peroxidase activity. The enzyme first converts Arachidonate into PGG2 via cyclooxygenase activity. Then it convert PGG2 to PGH2 via peroxidase activity.
Ibuprofen inhibit the cyclooxygenase activity by mimicking the structure of its substrate or some intermediate.
PGH2 is converted to many prostaglandins and thromboxanes. Prostaglandins can elevate fever, inflammation and pain.
COX have 2 main isozymes; COX-1 and COX-2. COX-2 is responsible for pain and hence inhibiting COX-2 can relive pain. Inhibiting COX-1 however leads to adverse effect in gastrointestinal tract.
Ibuprofen can exits in its 2 stereoisomeric forms ; R and S. They have different biopharmaceutical effects. The conformation of atoms and groups are different in R and S forms. So the binding and affinity of these stereoisomers will be different towards proteins that metabolize them. Many proteins could only metabolize either of the stereoisomer , but not both.
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