Chirality and Drugs

Most biomolecules namely proteins, carbohydrates and nucleic acids are chiral and exist in enantiopure forms.  When a chiral molecule (e.g. drug) interacts with a chiral biomolecule (e.g. protein), the resulting complex is diastereomeric.  Each enantiomer would form a different diastereomeric complex.  As discussed earlier diastereomers have different chemical and physical properties.  Thus each enantiomer would behave differently in the chiral environment of the biomolecule and each enantiomer of a drug can have different activities.

Two important drugs that can exist as R/S enantiomers are shown below. (S)-Ibuprofen is an active NSAID, while (R)-Ibuprofen is less effective. Ibuprofen is manufactured as a racemate (i.e. 1:1 mixture of the R and S enantiomers). At one point in history chemists considered synthesizing and marketing only the enantiopure (S)-Ibuprofen. It was later discovered that the inactive R form isomerizes in vitro and in vivo to the active (S)-Ibuprofen, negating the need to synthesize it enantiopure.

(R)-Ibuprofen              (S)-Ibuprofen

Thalidomide, sold under the brand names Contergan and Thalomid among others, is an oral medication used to treat a number of cancers (e.g. multiple myeloma), graft-versus-host disease, and many skin disorders (e.g. complications of leprosy such as skin lesions).[6][7][8] While thalidomide has been used in a number of HIV-associated conditions, such use is associated with increased levels of the virus.

(R)-Thalidomide                   (S)-Thalidomide