Table 1 List of antimalarial drugs along with their drug targets and site of action
Sl. no | Drug | Drug target/s and mechanism | Site of action | Refs. |
|---|---|---|---|---|
1 | Amodiaquine | Not known, but it is assumed that it inhibits heme polymerase activity. The amodiaquine-heme complex is toxic and disrupts the membrane function of the parasite | Food vacuole | [19] |
2 | Artemether | Inhibits nucleic acid and protein synthesis at erythrocytic stages of Plasmodium falciparum | Food vacuole | [20] |
3 | Artemisinin | Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) of P. falciparum Alkylation of essential malarial proteins and lipids | ER, vesicular structures | [21] |
4 | Atovaquone | Cytochrome bc1 complex (Complex III). Inhibits the parasite mitochondrial ETC pathway, resulting in the loss of mitochondrial function | Mitochondria | [22] |
5 | Chloroquine | Chloroquine inhibits hemozoin formation, leading to the accumulation of heme in the food vacuole. The free heme then lyses the membrane and leads to parasite death Inhibits DNA and RNA synthesis | Food vacuole | [23] |
6 | Clindamycin | Clindamycin is a lincosamide antibiotic that exerts antimalarial activities (against multidrug-resistant P. falciparum) when given in combination with quinine. It inhibits protein synthesis | - | [24] |
7 | Doxycycline | Doxycycline (an antibiotic) inhibits 30S ribosomal translation inside the essential apicoplast organelle, leading to parasite death It is also given with quinine | Apicoplast | [25] |
8 | Halofantrine | Halofantrine appears to inhibit heme polymerization, resulting in the parasite being poisoned by its waste It also acts as a blood schizonticide | RBC | [26] |
9 | Hydroxychloroquine | The exact mechanism is unknown. It is assumed that hydroxychloroquine acts similarly to chloroquine. In addition, it accumulates in the parasite lysosomes. It raises the vacuole's pH, leading to essential protein degradation and affecting the post-translation modification of proteins in the Golgi bodies | Food vacuole | [27] |
10 | Lumefantrine | The exact mechanism is unknown. It is assumed that it inhibits β-hematin formation by forming a hemin complex and inhibits protein and nucleic acid synthesis It also acts as a blood schizonticide and exerts effects against erythrocytic stages of Plasmodium spP | RBC | [28] |
11 | Mefloquine | The action of the mechanism is not entirely understood. A few reports suggest that it inhibits parasite protein synthesis through direct binding to the cytoplasmic ribosome (80S-ribosome) of P. falciparum, which leads to cause schizonticidal effects It damages the parasite’s membrane | Ribosome | [29] |
12 | Methylene blue | It inhibits P. falciparum glutathione reductase, which hampers the polymerization of heme into hemozoin (essential for parasite survival) | RBC | [30] |
13 | Piperaquine | The mechanism is similar to chloroquine. It inhibits the heme detoxification pathway of P. falciparum | Food vacuole | [31] |
14 | Primaquine | The mechanism is unclear. It interferes with the mitochondrial ETS pathway and destroys mitochondria | Mitochondria | [32] |
15 | Proguanil | Proguanil inhibits dihydrofolate reductase of the Plasmodium, which blocks the purine and pyrimidine biosynthesis. This inhibition leads to nuclear division failure at schizont formation in the liver and erythrocytes Inhibition of DNA synthesis | RBC, liver malaria: the past and the present | [33] |
16 | Pyrimethamine | Pyrimethamine inhibits dihydro-folate reductase (DHFR). The mechanism is similar to proguanil | RBC, liver | [34] |
17 | Pyronaridine | Under investigation. It is an erythrocytic schizonticide It binds with DNA and disturbs nucleic acid metabolism | RBC | [35] |
18 | Quinacrine | Under investigation. It binds with DNA and disturbs nucleic acid metabolism | RBC | [36] |
19 | Quinine | Purine nucleoside phosphorylase enzyme (inhibits the spontaneous formation of hemozoin) It inhibits protein synthesis and glycolysis. It acts as a blood schizonticide and has gametocytocidal activity against Plasmodium vivax and P. malariae | Digestive vacuole | [37] |
20 | Sulfadoxine | Sulfadoxine targets Plasmodium dihydropteroate synthase (it converts para-aminobenzoic acid to folic acid, which helps in nucleic acid synthesis) and dihydrofolate reductase (DHFR) proteins | Schizonts | [38] |
21 | Tafenoquine | The mechanism is not well established. It is assumed that it also inhibits heme polymerase (resulting in the parasite being poisoned by its waste) in the blood stage of the parasites | RBC | [39] |