# A Look at the Importance of Chirality in Drug Activity: Some Significative Examples
###### Abstract  
Chirality plays an important role in the development of many pharmaceuticals, being a general property of 'handedness'; nevertheless, a large number of pharmaceuticals are still marketed and administered as racemates. Chirality is all around and even within us; indeed, receptors and enzymes are chiral entities and interact in a specific manner with chiral drugs. Consequently, controlling enantiomeric purity and isolating the enantiomers from chiral drugs remains a crucial subject for analytical, clinical, and regulatory purposes, thus, improving the drug safety profile. The classical examples of spontaneous enantiomerization and severe toxicity related to chirality are represented by ibuprofen and thalidomide, respectively, but numerous other cases have been reported in the literature. This review intends to offer a brief overview on the most common chiral drugs used in therapy for the treatment of various diseases. chirality; asymmetry; enantioseparation; etutomer; distomer; chiral drugs +
Footnote †: journal: Medical  
a racemic mixture (Figure 1). In this context, chirality has become a significant challenge in the synthesis and development of drugs [10]. Different methods have been used to obtain the single enantiomers, which make use of resolution procedures, enantioselective syntheses, and enantioselective analytical approaches [11; 12; 13; 14; 15; 16]. Specifically, enantioselective gas chromatography [17; 18], supercritical fluid chromatography [19], high performance liquid chromatography [20; 21], ligand-exchange chromatography [22], and chiral electrochromatography [23] are used. Recently, molecularly imprinted technique (MIT) has received wide consideration for the separation of racemates due to its simple operations [24]. Moreover, chiral metal-organic frameworks (CMOF) materials are commonly used for chiral recognition, separation, and catalysis [25]. More new methods for isolation of enantiomers and control of their enantiomeric purity have been proposed [26; 27]; however, given the high cost of enantioselective syntheses [28; 29] or the separation of enantiomers [30; 31], the racemic mixtures of chiral drugs are still often used in therapy. It has also to be considered that the determination of the exact 3D structure of drug candidates is of foremost importance for the pharmaceutical industry in different stages of the discovery [32]. A growing interest of chirality in the exploration of 3D chemical space and modern drug discovery approaches have been recently reported for the high throughput hit identification (hit-ID) [33]. In 1999, [PERSON] and [PERSON] introduced the term \"chiral switch\", which was then modified and refers to the development of a single enantiomer from a chiral drug, previously approved and marketed as a racemate or as a mixture of diastereoisomers [34; 35]. Chirality may also influence metabolism of drugs; indeed, it may happen that the metabolite of one enantiomer can be more active than the other isomer [36; 37]. Thalidomide is often used as the classical example of a drug that cannot be used as a racemic mixture, given the toxicity of the distomer [38], even though this assumption has been challenged by some authors [39]. Thalidomide was a drug first used for relief of morning sickness in pregnant women, but then it was withdrawn from the market for its dramatic effects on normal fetal development. Toxicity of thalidomide was demonstrated to be related to the distomer and the (\(S\))-isomer, while the (\(R\))-enantiomer represented the eutomer [40]. [PERSON] et al. reported  
Figure 1: Advantages in the use of single enantiomer drugs. a capillary electrokinetic chromatography study for the enantiomerization of thalidomide [41]. For this purpose, the drug repositioning, which consists of identifying and studying new uses for existing or abandoned pharmacotherapies, is a very useful approach for developing drugs for the treatment of several diseases with lower overall costs and shorter development timelines, is of help [42, 43].