What is the Difference Between Isosteres and Bioisosteres

The key difference between isosteres and bioisosteres is that isosteres are molecules or ions with similar shapes and electronic properties, whereas bioisosteres are biologically active compounds consisting of an isostere.

Isosteres and bioisosteres are two related concepts. Isosteres can be described as any molecules or ions having the same number of valence electrons and having chemical or physical similarities. Bioisosteres are chemical substituents or groups having similar physical or chemical properties producing broadly similar properties to another chemical compound. These two terms are mainly used in the context of bioactivity and drug development.

1. Overview and Key Difference
2. What are Isosteres
3. What are Bioisosteres
4. Isosteres vs Bioisosteres in Tabular Form
5. Summary – Isosteres vs Bioisosteres

What are Isosters?

The term isostere refers to chemical species having a similar size, the same number of atoms, and the same number of valence electrons. The chemical species we are considering in this context are molecules or ions. For example, benzene and thiophene are isosteric molecules. Generally, isosteric molecules have the same shape because of their identical electron arrangements. Often, these chemical species have similar electronic properties as well.

Isosteres and Bioisosteres - Side by Side Comparison

Figure 01: Silafluofen is an Isostere of Pyrethroid Insecticides

The concept of isosteres was first developed by Irving Langmuir in 1919. Later, it was modified by Grimm. Biologically-active compounds that contain an isostere are known as bioisosteres.

What are Bioisosteres?

Bioisosteres are chemical substituents or groups having similar physical or chemical properties producing broadly similar properties to another chemical compound. These compounds are important in medicinal chemistry and drug design. In the process of drug design, exchanging one bioisostere for another is done to enhance the desired biological or physical properties of a compound in such a way any significant changes are not made to the chemical structure.

Bioisosteres are mainly used for reducing toxicity, changing bioavailability, or modifying the activity of the lead compound. It can also alter the metabolism of lead. When considering classical bioisosterism, this concept was originally formulated by James Moir and later refined by Irving Langmuir. This was a response to the observation that different atoms having the same valence electron structure have the same biological properties.

Isosteres vs Bioisosteres in Tabular Form

Figure 02: Some Common Classical Bioisosteres

For example, replacing a hydrogen atom with a fluorine atom at the site of metabolic oxidation in a drug candidate can prevent this type of metabolism from happening. The size of the fluorine atom is similar to the size of the hydrogen atom. Therefore, the overall topology of the molecule is not affected considerably. This leaves the desired biological activity unaffected.

What is the Difference Between Isosteres and Bioisosteres?

Isosteres and bioisosteres are related compounds. The key difference between isosteres and bioisosteres is that isosteres are molecules or ions with similar shapes and electronic properties, whereas bioisosteres are biologically active compounds consisting of an isostere. Some examples of isosteres include SH, NH2, and CH3 while aromatic rings, aminopyrine, estradiol, dienestrol, etc. are examples of bioisosteres.

The following table summarizes the difference between isosteres and bioisosteres.

Summary – Isosteres vs Bioisosteres

The term isostere refers to chemical species having a similar size, the same number of atoms, and the same number of valence electrons. Bioisosteres are chemical substituents or groups having similar physical or chemical properties producing broadly similar properties to another chemical compound. The key difference between isosteres and bioisosteres is that isosteres are molecules or ions with similar shapes and electronic properties, whereas bioisosteres are biologically active compounds consisting of an isostere. Overall, these two terms are mainly used in the context of bioactivity and drug development.

Reference:

1. “Bioisostere.” An Overview | ScienceDirect Topics.
2. “Isostere.” Wikipedia. Wikipedia Foundation.

Image Courtesy:

1. “Silafluofen” By Ed (Edgar181) – Own work (Public Domain) via Commons Wikimedia
2. “Classical bioisosteres 2” By Iandoxsee – Own work (CC BY-SA 4.0) via Commons Wikimedia