Bioisosters are substituents or groups with similar physical or chemical properties that produce broadly similar biological properties to other chemical compounds. The relation between bioisosteres is known as bioisosterism
In drug design, exchanging one bioisoster for another enhances a compound’s desired biological or physical properties without making significant changes in chemical structure. For example
Bioisosters are used to reduce toxicity or modify the activity of a lead compound and may alter the metabolism of the lead. Bioisosters have the same number of atoms and the same number of electrons; the electrons may arrange themselves in the same manner.
Bioisosterism in molecular modification:
Langmuir first developed the concept of chemical disasters to describe the physical properties of atoms, functional groups, and molecules. A compound or group of atoms having a same number of atoms and electrons.
Burger defines bioisosters as substituents or groups with similar chemical and physical properties that produce broadly similar biological properties.
Why bioisosteric replacement:
The size, shape, electronic effect, lipid solubility, water solubility, Pka, chemical reactivity, and hydrogen bonding are the parameters that influence potency, selectivity, and duration of action. Bioisosterism is effective because it affects all the above parameters to a lesser or greater extent.
Classification of Bioisosters:
Basically bioisosters are two types-
- Classical bioisosters
- Non-classical bioisosters.
Classical bioisosters:
Classical bioisosters are molecules having similar shapes and electronic properties. These commonly conserve the same structural properties. These are the following subtypes –
Non-classical bioisosters:
They do not have a same number of atoms & do not fit the series and electronic rules of classical isosteres. But produce similar biological activity. For example-
Halogens [Cl, Br, F, I]
Ethers [R-O-R, R-S-R]
Hydroxy group [ -OH]
Carboxylic group [R-COOH, R-SOOH]
