Table 1.
Modes of action and resistance mechanisms of commonly used drugs in ACTs.
| Drug | Class | Site of action | Mode of action | Molecular markers of resistance |
|---|---|---|---|---|
| PPQ | 4-Aminoquinoline | FV | Interfere with Hb digestion & heme detoxification | Plasmepsin 2 & 3 amplification, NS SNPs in PfCRT |
| AQ | 4-Aminoquinoline | FV | Interfere with heme detoxification | NS SNPs in PfMDR1 & PfCRT |
| MQ | Arylamino alcohol | FV & cytoplasm | Interfere with Hb uptake & heme detoxification; target the pf80S ribosome, purine nucleoside phosphorylase, and PfMDR1 |
Pfmdr1 amplification, NS SNPs in PfMDR1 & PfCRT |
| LMF | Arylamino alcohol | FV & cytoplasm | Interfere with Hb uptake & heme detoxification; target PfMDR1 |
Pfmdr1 amplification, NS SNPs in PfMDR1 & PfCRT |
| ARTs | Endoperoxide | Cytoplasm | Induce oxidative stress, proteasomal stress, DNA damage; alkylate and oxidate proteins, lipids, and heme | NS SNPs in K13, UBP-1, AP2-μ, Coronin, Eps15, Falcipain 2a |
Abbreviations: Piperaquine (PPQ), amodiaquine (AQ), mefloquine (MQ), lumefantrine (LMF), artemisinins (ARTs), food vacuole (FV), hemoglobin (Hb), Nonsynonymous single nucleotide polymorphisms (NS SNPs), P. falciparum chloroquine resistance transporter (PfCRT), P. falciparum multidrug resistance gene-1 (Pfmdr1), Kelch 13 (K13), ubiquitin-binding protein-1 (UBP1), adaptor protein-2μ (AP-2μ), epidermal growth factor receptor substrate-15 (Eps15) homolog.