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Table 1 Date of introduction and first reports of anti-malarial drug resistance, resistance genes involved [33, 86, 87] and main mechanisms of resistance

From: Plasmodium falciparum: multifaceted resistance to artemisinins

Anti-malarial drug Introduced First reported resistance Resistance genes Main resistance mechanisms Refs
Quinine 1632 1910 Pfmdr1/other Disruption of drug accumulation inside the food vacuole by reduced propensity of the drug transporter PfMDR1 to bind to and transfer the anti-malarial [88, 89]
Chloroquine 1945 1957 Pfcrt/Pfmdr1 Drug extrusion on from digestive vacuole by mutated drug transporter PfCRT due to higher lipophilicity and negativity of the transporter allowing ionized chloroquine efflux [9092]
Proguanil 1948 1949 Pfdhfr Modification of the drug target: reduced inhibition of enzymatic activity by the drug [9]
Sulfadoxine-pyrimethamine 1967 1967 Pfdhps-Pfdhfr
Mefloquine 1977 1982 Pfmdr1/other Reduction of parasite susceptibility to mefloquine by amplification of Pfmdr1 copy number [93]
Atovaquone 1996 1996 Pfcytb Modification of the drug target by disruption of Cytochrome bc1 complex [8]
Artemisinins 1980s 2006 Pfk13 Quiescence [31, 33]