Classification of Antimalarial Drugs
- BP-S-6-Medicinal Chemistry III
- Mar 28
- 1 min read
Antimalarial drugs are classified based on their chemical structure and mechanism of action. The main classes include:
1) Quinolines
These are synthetic or natural compounds that interfere with the parasite's ability to digest hemoglobin.
Examples: Quinine sulphate, Chloroquine, Amodiaquine, Primaquine phosphate, Pamaquine, Quinacrine hydrochloride, Mefloquine.
Structural Feature | SAR Insight |
Quinoline nucleus (1- or 4-substituted) | Essential for antimalarial activity. Most active compounds are 4- or 8-aminoquinolines. |
Position 4 (4-amino group) | Common in chloroquine and amodiaquine; important for blood schizonticidal activity. |
Position 8 (8-amino group) | Seen in primaquine, pamaquine; responsible for tissue schizonticidal and gametocidal action. |
Side chain on amino group | Chain length (typically 3 C atoms) is critical. Bulky or very long chains reduce activity. |
Position 6 (methoxy or other substitutions) | Methoxy or halogen (Cl, Br) often improves lipophilicity and activity (e.g., in primaquine, amodiaquine). |
Electron-donating groups on ring | Increase antimalarial activity and reduce toxicity. |
Electron-withdrawing groups on ring | Often reduce activity. |
Basic nitrogen in side chain | Enhances accumulation in the acidic food vacuole of the parasite. Protonation helps trap the drug. |
Hydroxylation or polar groups | May reduce blood stage activity but are tolerated in tissue stage drugs (e.g., primaquine). |
2) Biguanides and Dihydrotriazines
These drugs act by inhibiting dihydrofolate reductase (DHFR), which is essential for the parasite's DNA synthesis.
Examples: Cycloguanil pamoate, Proguanil.
3) Miscellaneous
This group consists of antimalarial agents with varied mechanisms, such as inhibiting mitochondrial electron transport, disrupting heme detoxification, or acting on parasite protein synthesis.
Examples: Pyrimethamine, Artesunate, Artemether, Atovaquone.
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