Chemical Basis for Drug Action

What is a drug?

A chemical substance of known structure that produces a biological effect when administered to a living organism.

What can drugs be used for?

To treat, cure, prevent, or diagnose disease or promote well-being.

What type of compound is a drug usually?

An organic compound.

What is a drug target?

A molecule in the body associated with a disease process that can be acted upon by a drug to produce a desired therapeutic effect.

What must a drug do to produce a therapeutic effect?

Bind to its target.

What happens when a drug (I) binds to its target (E)?

It forms a drug-target complex (E–I).

What can formation of the drug-target complex do to the target?

Change the conformation of the target.

How does the energy of the drug-target complex compare with a free drug + free target?

The drug-target complex has lower energy.

What is a covalent bond?

A chemical bond involving the sharing of electron pairs between atoms.

Do most drugs form covalent bonds with their biological targets?

No. Only a small number of drugs act by forming covalent bonds with their targets.

Are covalent drug-target bonds readily reversible?

No. They cannot be readily reversed.

Why can covalently bound drugs have a long duration of action?

Because the strong covalent bond cannot be readily reversed.

What is a potential problem with the specificity of covalently bound drugs?

Specificity may be low, potentially producing prolonged adverse effects.

What are the four covalent drug-target mechanisms

• Alkylation

• Acylation

• Phosphorylation

• Rearrangement

What is alkylation?

A drug adds an alkyl group (CₙH₂ₙ₊₁–) to its target.

What DNA base can be targeted during drug alkylation?

Guanine

What is a major clinical use of alkylating agents?

Cancer treatment

What do alkylating antineoplastic agents do?

Inhibit tumor growth.

What is acylation?

A drug adds an acyl group (RCO–) to its target.

What functional groups may be present in drugs that undergo acylation?

• Ester

• Lactone

• Amide

• Carbamate

How do β-lactam antibiotics produce antibacterial activity?

By acylating DD-transpeptidase.