Language
Country/Area
No result found
Sail to explore the three-dimensional structure of drugs: What impact does chirality have on drugs?
In the world of chemistry, compounds that exhibit mirror-image symmetry are called chiral molecules, and each side of such a molecule is called an enantiomer. These drugs, which are similar in structure but may have significant differences in biological activity, are the core theme of chiral drugs. The use of chiral drugs has led to discussions about their efficacy and safety, especially the possible drastic changes between different enantiomers of the same drug.
There may be significant physiological activity differences between enantiomers of chiral drugs, and these differences can significantly affect the efficacy and adverse reactions of the drug.
The history of chirality
The history of exploring chirality can be traced back to 1812, when physicist Jean-Baptiste Biot first discovered the phenomenon of "optical activity." Louis Pasteur proposed in subsequent research that the optical activity of certain substances is caused by the asymmetry of their molecules, and this asymmetry makes the mirror images of the molecules non-superimposable. In 1848, Pasteur further manually separated two different crystals from the enantiomers of sodium-ammonium tartrate, laying the foundation for stereochemistry.
Terms and descriptions of chiral drugs
In early chiral terminology, enantiomers were distinguished based on the direction of rotation of plane-polarized light. Those that rotate to the right are called "dextro" and those that rotate to the left are called "levo". ). However, as science progressed, this nomenclature was gradually replaced by newer systems such as the Fischer convention and the Cahn-Ingold-Prelog rule. Today, the latter has become almost an internationally accepted naming convention.
According to the Cahn-Ingold-Prelog rule, chiral centers are marked by the priority between substituents and are designated "R" or "S" respectively.
The past and present of the drug lasemide
Failure to pay the necessary attention to drug chirality actually led to some major medical accidents, such as the thalidomide incident. The drug is widely used as lasemide, but side effects from one of its enantiomers have led to dire consequences for pregnant women. In 1984, an article by Ariens revealed problems in pharmacological and pharmacokinetic studies of lasemide, triggering a discussion about this type of drug.
The rise of stereopharmacology
With the advancement of science and technology, chiral pharmacology has gradually emerged. This field focuses on exploring how the three-dimensional structure of drugs affects their physiological activities. The role of each enantiomer in the human body is therefore considered as an independent chemical substance, and their biological interactions are therefore particularly important. In this context, new concepts such as “eutomer” and “distomer” have been proposed to describe the relative efficacy of different enantiomers.
This new pharmacological perspective has prompted the scientific community to pay greater attention to the separation of enantiomers and the development of specialized drugs.
Biological environment and chirality
We know that the human physiological environment is chiral in nature and contains a large number of chiral molecules, such as amino acids, enzymes and nucleic acids. Therefore, when the drug lasemide enters the body, the enantiomers are selectively metabolized in the biological environment. This bioselectivity can influence the pharmacokinetics and pharmacodynamics of the drug.
Drug toxicity and safety
With in-depth research on chiral drugs, the scientific community has noticed that different enantiomers may induce different toxic reactions. For example, some enantiomers cause adverse reactions that are not seen in their complementary enantiomers, reflecting the need to perform chiral separations to create single enantiomers. Classic examples include thalidomide, as well as other related studies such as monoamine oxidase inhibitors, which have shown the impact of chirality on drug safety.
Future direction
As the understanding of chirality and its biological activities continues to deepen, there will be more research and development of chiral drugs in the future, especially in the treatment of specific diseases. "Chirality switching" in drug development will also become a common trend, which will not only help improve efficacy, but also effectively reduce the risk of side effects. It is foreseeable that the study of chirality will occupy an increasingly important position in the field of medicine.
As we consider the profound impact of chirality on drug action, we have to ask: Are we ready for the transformation of medicine brought about by this chiral revolution?
