How to keep the drug active and give full play to its therapeutic effect has always been the primary problem to be solved by researchers in the field of pharmacy. It is a very complex process from drug administration to the generation of drug efficacy. Scientists have divided this process into three phases: Pharmaceutical phase, pharmacokinetic phase and pharmacodynamic phase. Only by ensuring the entire process is error-free, can researchers devoted to discovering new drugs eventually obtain the ideal drug with safety, effectiveness and controllability. The activity and efficacy of drugs are closely related to the chemical structure of drugs, which is called structure-activity relationship (SAR). Therefore, during drug discovery and drug design, researchers will inevitably pay attention to the relationship between the structure and efficacy of drugs.
Classification of Drugs
According to the structure and the way drugs work in the body, they can be divided into two categories: structure nonspecific drugs and structure specific drugs. The receptor theory believes that drugs can only produce drug activity after binding to receptors, and their needs for receptors are different. Structure nonspecific drugs do not interact with particular receptors and have no special requirements on the chemical structure of drugs. However, there are only a few drugs belonging to this category, the most common one of which is inhalation anesthetics in general anesthetics. However, structure specific drugs need to combine with particular receptors to form complexes. And a slight diversity in the structure of drugs may lead to a huge change in the activity. At present, researchers can detect the relationship between drugs and receptors through virtual screening technology so as to ensure the drug activity.
Effect of Pharmacophores
Since only the interaction between drugs and receptors can produce drug activity, drug molecules must first have the properties and structures that can combine with corresponding receptors. These structures include electrical structure and three-dimensional structure, which are collectively regarded as pharmacophores. By using pharmacophore model construction and other technologies, scientists can introduce different functional groups into drugs to change the molecular structure, so as to learn about the binding of drugs with receptors and drug efficacy. For example, the introduction of alkyl groups can promote the hydrophobic binding. And drugs containing amides can combine with biological macromolecules to form hydrogen bonds, thus enhancing the binding with receptors and the activity of drugs.
Influence of Bonding
Drugs interact with receptors and form complexes through a variety of bonding methods. Among them, the covalent bond is the strongest one between drugs and receptors, and it is irreversible as well. Most of the anti-infective drugs, such as penicillin, which is often mentioned by people, are combined with biological enzymes through covalent bonds, thus producing irreversible inhibitory action, which can play an efficient and sustained antibacterial effect. But the bonding methods other than covalent bonds are weak, so their effect is reversible, and the drugs can only play its therapeutic role in a limited time. In accordance with the structure of drugs, a variety of bonding methods can be applied, but generally speaking, during the preparation of drugs, researchers will not use only one but multiple bonding methods to form a reversible complex.
The relationship between the chemical structure and the activity of drugs is one of the most important contents in the pharmaceutical chemistry research. Only by fully mastering the influence of different chemical structures on drug activity and the conditions for drug efficacy, can scientists develop new drugs to treat more diseases faster and better. With the continuous improvement of quantum chemistry and computer-aided drug design (CADD), various technologies, such as molecular dynamic simulation and QM/MM simulation, have gradually matured to further help researchers make breakthroughs in this field.
