Posts Tagged ‘chiral’

Drug Structural Effects on Living Cells

Author: Danut Dragoi, PhD

Most drugs have the chemical composition of light chemical elements, C, H, N, O, S in such combination that determines a unique molecular structures for a given molecular weight value. It is interesting that drug structures include chiral handedness which plays an important role in therapeutics.

Drugs development went in advanced stages in which the therapeutic effects can be predicted and matched with any disease before it is made. However, the science of matching a drug to a curable disease is pretty much a pragmatic activity that is based on trials and observations. The medical trails are needed as a safe method before the drug is released to the public. Drug’s structures, and their fragments are discusses in here.

An interesting example of drug chirality effects on human living cells is Ethambutol, which exists in two chiral forms, the (S,S)-(+)-enantiomer that is used to treat tuberculosis, and the (R,R)-(–)-ethambutol that causes blindness, a significant side effect [1] .

The picture below shows the two enantiomers of Ethambutol, L and D forms, adapted to illustrate the mirror symmetry on a plan placed between the two molecules.

L and D ethambutol

Image  SOURCE: adapted from http://www.chemspider.com/Chemical-Structure.412943.html?rid=f51c3f22-3f31-4a7e-9d55-64469464ccf4. NB: the envelope on each enantiomer is a molecular orbital representation of electron density which plays an important role on metabolic reactions in human body.

About 56% of the drugs currently in use are chiral products, showing the importance of chirality on designing drugs today.

Chiral S- and R- drugs

Examples of other enantiomers with important action effects on human body is abundant in literature. For example enantiomers of a chiral drug have identical physical and chemical properties in an achiral environment. In a chiral environment, one enantiomer may display different chemical and pharmacological behavior than the other enantiomer. Because living systems are themselves chiral, each of the enantiomers of a chiral drug can behave very differently in vivo. In other words, the R-enantiomer of a drug will not necessarily behave the same way as the S-enantiomer of the same drug when taken by a patient. For a given chiral drug, it is appropriate to consider the 2 enantiomers as 2 separate drugs with different properties unless proven otherwise.

The increasing availability of single-enantiomer drugs promises to provide clinicians with safer, better-tolerated, and more efficacious medications for treating patients. It is incumbent upon the practicing physician to be familiar with the basic characteristics of chiral pharmaceuticals discussed in this article. In particular, each enantiomer of a given chiral drug may have its own particular pharmacological profile, and a single-enantiomer formulation of a drug may possess different properties than the racemic formulation of the same drug. When both a single-enantiomer and a racemic formulation of a drug are available, the information from clinical trials and clinical experience should be used to decide which formulation is most appropriate.





[1] Padmanabhan, Deepak. “A review of drug isomerism and its significance”. US National Library of Medicine National Institutes of Health. pp. 16–18. doi:10.4103/2229-516X.112233. Retrieved 16 April 2016.





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