Pamaquine (Plasmochin): Structure, SAR, Synthesis, Mechanism of Action, Uses & Side effects

Chemical formula:

• C19H23N3O

Structure of Pamaquine

Structure-Activity Relationship (SAR):

• The 8-aminoquinoline core structure is essential for the antimalarial activity of pamaquine. This core structure is crucial for the activity against the liver stages of the malaria parasite.\

• The terminal diethylamino group in the side chain plays a significant role in the drug's activity. Like in chloroquine, this group is thought to be protonated under the acidic conditions within the parasite's digestive vacuole, leading to drug accumulation.

• Alterations in the side chain or the 8-amino group can cause changes in the drug's antimalarial activity. For example, changes in the length of the side chain can affect the drug's activity and toxicity.

Here is the diagram illustrating the Structure-Activity Relationship of Pamaquine (Plasmochin):

Synthesis:

• Pamaquine synthesis starts with the reaction of 1-chloro-4-pentanone with dimethylamine, followed by a condensation with 8-aminoquinoline.

Step: (1) C5H9ClO + (CH3)2NH → C5H11NO + (CH3)2NCl

Step: (2) C5H11NO + C9H7N → C14H16N2O

• The first step is a nucleophilic addition of dimethylamine to 1-chloro-4-pentanone. The second step is a condensation of the resulting product with 8-aminoquinoline.

Mechanism of action:

• Pamaquine's exact mechanism is unclear, but it is thought to generate reactive oxygen species that damage the parasite's cellular structures.

Uses:

• Pamaquine was historically used to treat relapsing malaria caused by P. vivax and P. ovale.

• However, it has been largely replaced by prima.