Chiral Drugs

Jermaine P. Serrano
Drug chirality is now a major theme in the design, discovery, development, launching and
marketing of new drugs. The human body is made up of chiral receptors. Chirality in the human
body makes it selectively affinitive to the drugs being introduced to the body. Chiral drugs have
enantiomers that affect its therapeutic efficiency. Most of the chiral drugs made nowadays are a
mixture of enantiomers. That is, it is most probable that each enantiomer or the drug will exhibit
different physiological effects. It is important to know whether both enantiomers of a drug
exhibit desirable effect or if one exhibits harmful effect and the other does not.
A chiral carbon is an sp3 carbon atom with four unidentical groups attached to it. This is a type of
molecule that has a non-superposable mirror image. The presence of an asymmetric carbon atom
is often the feature that causes chirality in molecules. A chiral carbon should have an enantiomer.
An enantiomer is one of two stereoisomers that are mirror images of each other that are nonsuperposable, much as one's left and right hands are the same except for opposite orientation.
In a more scientific definition by Evans ( 2014), Enantiomers are molecular entities which are
non-superimposable mirror images. The chirality (handedness) of enantiomeric molecules is
caused by the presence of one or more chiral elements (chirality axis, chirality plane, or chirality
centre, e.g., asymmetric carbon atom) in the structure. The chirality and optical activity of the
enantiomers is determined by their absolute configuration, i.e., the spatial arrangement of the
atoms in the molecule.
Two enantiomers of the same compound, despite having the same physical and chemical
properties, show different interactions with other chiral molecules due to differences in spatial
arrangement of the atoms and therefore binding affinity. This phenomenon is particularly
significant in biological interactions as all proteins, enzymes and carbohydrates are chiral. Thus
organisms might respond uniquely to each enantiomer.
Majority of the receptors in the human body is chiral. Thus, a chiral receptor can only bind with
one pair of an enantiomer. According to Tian (2012), Chiral drugs, which took more than 50%
of all current drugs, have been paid more and more attention for their clinical applications. A pair
of enantiomers would be discriminated as different molecules by chiral environment such as
enzymes, receptors, carries, etc. Bio membrane permeability and cellular uptake of chiral drugs
may be also stereo selective if intracellular macromolecules recognize the enantiomers in chirally
discriminative ways. Therefore, the pharmacodynamics, pharmacokinetics and toxicology
between the enantiomers could be stereoselective.
The drugs are categorized into three classes: natural products a chemical compound or
substance produced by a living organism found in nature; natural products that have been
modified in the laboratory; synthetic compounds produced by chemical synthesis, especially
not of natural origin. Most drugs obtained from natural sources consist of a single enantiomer.
Most of the drugs being produced nowadays are a mixture of enantiomers. The biological
response produced by enantiomers is rarely similar. There is an evidence that the human body is
capable of converting R enantiomer into desired S enantiomer. Jamalis (1997) study found the
following: The R enantiomers of some of the 2-arylpropionic acid non-steroidal

antiinflammatory drugs (NSAIDs) are known to undergo metabolic chiral inversion to their more
pharmacologically active antipodes. This process is drug and species dependent and usually
unidirectional. The S to R chiral inversion, on the other hand, is rare and has been observed, in
substantial extents, only for ibuprofen in guinea pigs and 2-phenylpropionic acid in dogs.
Although the research is conducted to animals, the same phenomenon was also observed in
humans.
Chiral carbons have different affinities and so as the receptors in the body. Hence, chiral drugs
and its enantiomers will either react or not to the receptors. This highly selective affinity of the
receptor and the chiral drugs greatly affects its therapeutic efficiency. Every so often, an
enantiomer reacts undesirably, thus, the creators of the drug separates the enantiomer and
consequently making a drug a single-enantiomer drug. Single-enantiomer drugs are highly
efficient but the production is pricey. According to Mansfield ( 2004), Most new drugs are
marketed as single enantiomers but many older agents are still available in racemic form. As
these drugs reach the end of their patent life manufacturers become interested in marketing single
enantiomer equivalents. This is called chiral switching and it has been claimed that it will bring
clinical benefits in terms of improved efficacy, more predictable pharmacokinetics or reduced
toxicity. Single-enantiomer drug is more effiecient than that of the racemic one because it
contains a single kind of enantiomer. I.e., more enantiomer affinitive to the receptor it was made
to bind will be able to adhere to it.
Chirality plays an important role in ones vigor. The efficacy of a drug depends on the chirality of
both the human body receptor and the drug itself. Enantiomers of a chiral drug can either benefit
or harm the consumer. In cases where in the enantiomer can harm the consumer, the drug can be
purified into a single-enantiomer drug. This kind of drug is said to be more efficient than that
of the racemic one.

Bibliography
Evans, K.-H. (2014). Applications of chiral chromatography coupled with mass spectrometry in the
analysis of chiral pharmaceuticals in the environment. Elsevier, e34-e51.
Guo, T. H. (2011). Analysis of chiral non-steroidal anti-inflammatory drugs flurbiprofen, ketoprofen and
etodolac binding with HSA. Elsevier, 184-190.
Jamali, L. A. (1997). Bi-directional chiral inversion of ketoprofen in CD-1 mice. Pubmed, 29-31.
Mansfield, H. T. (2004). Single-Enantiomer Drugs. Clinical Pharmacokinesis, 287-290.
Tian, H. H. (2012). Determination of the enantioselectivity of six chiral aryloxy aminopropanol drugs
transport across Caco-2 cell monolayers. Elsevier, 168-173.