top of page
Search

Chloroquine*

Chemical Structure / Formula of Chloroquine*

  • Formula: C18H26ClN3

  • Structure: 4-Aminoquinoline with an ethyl-diethylamine side chain.

Chloroquine*

Mechanism of Action

  • Inhibits heme polymerase, preventing detoxification of toxic free heme, leading to Plasmodium death.

  • Accumulates in the food vacuole of Plasmodium spp.

Uses

  • First-line for non-resistant Plasmodium spp. (P. vivax, P. ovale, P. malariae).

  • Autoimmune diseases (RA, lupus: due to immunomodulatory effects).

Side Effects

  • Retinopathy (bull’s eye maculopathy): irreversible.

  • Pruritus (especially in dark-skinned individuals).

  • GI disturbances, QT prolongation, hemolysis in G6PD deficiency.

Structure-Activity Relationship (SAR) of Chloroquine

Structural Feature

Role in Activity

4-Aminoquinoline ring

Essential pharmacophore for antimalarial activity.

Basic side chain (diethylaminoalkyl)

Crucial for accumulation in acidic food vacuole of the parasite. Chain length affects potency (typically 3 carbon atoms in linker is optimal).

Electron-donating groups on aromatic ring

Can improve potency and reduce toxicity.

Halogen substitution (e.g., Cl at position 7)

Enhances lipophilicity and improves penetration into parasitic vacuole.

N-alkylation of side chain

Small alkyl groups tolerated; bulky substituents reduce activity.

Synthesis of Chloroquine

Synthesis of Chloroquine


bottom of page