Chloroquine: Structure, Structural Activity Relationship, Mechanism of Action, Uses & Side effect

Chemical formula:

• C18H26ClN3

Structure of Chloroquine

Structure-Activity Relationship (SAR):

• The 4-aminoquinoline core structure is crucial for chloroquine's antimalarial activity. Specifically, the 4-amino group is thought to interfere with heme detoxification within the parasite.

• The terminal diethylamino group of the side chain is another important feature. This group is thought to be protonated under the acidic conditions within the parasite's digestive vacuole, leading to the accumulation of the drug within the parasite.

• The presence of the chlorine atom at the 7th position in the quinoline ring is crucial for activity.

Here is the diagram illustrating the Structural Activity Relationship of Chloroquine:

Synthesis:

• Chloroquine is typically synthesized in a multi-step process starting from 4,7-dichloroquinoline and 4-diethylamino-1-methylbutylamine.

C9H5Cl2N + C8H22N2 → C18H26ClN3

• The reaction involves the substitution of the chlorine atom in 4,7-dichloroquinoline with the 4-diethylamino-1-methylbutylamine.

Mechanism of action:

• Like quinine, chloroquine inhibits heme detoxification within the Plasmodium food vacuole, leading to the accumulation of toxic heme and parasite death.

Uses:

• Chloroquine is used to treat P. vivax, P. ovale, and P. malariae infections, as well as chloroquine-sensitive P. falciparum malaria.

• It is also used for malaria prophylaxis in certain areas.

Side effects:

• Nausea

• Vomiting

• Diarrhea

• abdominal pain

• headache

• dizziness

• blurred vision

• and itching.

• Rare but serious side effects include QT interval prolongation, seizures, and severe skin reactions.