Chemical formula:
C18H26ClN3
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.
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.