Action of Anti-Cancer Drugs

Specification Reference Organic chemistry, Amino acids, proteins and DNA 3.3.13.5

Quick Notes

Prevents DNA replication in cancer cells by binding to guanine bases in DNA.
Works via ligand substitution where cisplatin’s chloride ligands are replaced by nitrogen atoms in guanine.
Adverse effects include damage to healthy cells. The benefits of treating cancer must be balanced against these adverse effects.

Cisplatin has the formula [Pt(NH₃)₂Cl₂].

It is a square planar complex with two ammonia (NH₃) ligands and two chloride (Cl⁻) ligands in a cis arrangement.

Cisplatin enters cancer cells and undergoes ligand substitution.

Inside the cell, the chloride concentration is lower than in blood, causing Cl⁻ ligands to be replaced by water.

This activated form of cisplatin binds to nitrogen atoms on guanine bases in DNA, forming a platinum–DNA complex.

This prevents DNA from unwinding and replicating, stopping cancer cell division.

A nitrogen atom in the guanine base forms a co-ordinate bond to the Pt, acting as a ligand and replacing one of the newly substituted water ligands.

Cisplatin significantly increases cancer survival rates.

Despite severe side effects, it is often used when the benefits outweigh the risks.

Ongoing research aims to develop less toxic platinum-based drugs.

Cisplatin is a square planar Pt(II) complex, [Pt(NH₃)₂Cl₂].
In cells, low chloride concentration leads to water molecules replacing chloride ligands; the activated complex binds to nitrogen atoms in guanine in DNA.
Pt–DNA coordination prevents DNA from unwinding and replicating, inhibiting cell division.
Therapeutic use requires weighing anti-cancer benefits against adverse effects on healthy cells.
Research continues into less toxic platinum drugs with improved selectivity.