Bioactivity Comments

The interaction table below provides data from an evaluation of the antimalarial (asexual blood stage) activity of amodiaquine, using a panel of P. falciparum strains. Note that much of the bioactivity associated with amodiaquine relates to use of various hydrochloride salt and hydrate forms. Amodiaquine is reported to rescue SARS-CoV-2 infected Vero-E6 cells from death, with an EC50 of 5 μM in a plaque assay [4]. Amodiaquine is one of a number of drugs that are cationic amphiphilic in nature, for which anti-SARS-CoV-2 activity has been identified in drug repurposing screens. Tummino et al. (2021; bioRxiv preprint PMID: 33791693 target="_blank") suggest that this antiviral activity is most likely a result of the drug promoting phospholipidosis via disruption of lipid homeostasis.

Whole organism assay data
Key to terms and symbols	Click on species/strain names for details	Click column headers to sort
MOA/likely target Sp. Assay description Type Action Value Parameter Concentration range (M) Reference Unknown MOA PfNF54 Plasmodium falciparum NF54 P. falciparum strain NF54 (PfNF54) was derived from a patient who had never left the Netherlands. PfNF54 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is sensitive to a panel of antimalarial compounds including chloroquine and pyrimethamine. ✖ Parasite growth inhibition assay - - 8.4 pIC50 - 3 ⤷ pIC50 8.4 (IC50 3.9x10-9 M) [3H]-hypoxanthine incorporation [3] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) Unknown MOA PfD6 Plasmodium falciparum D6 P. falciparum strain D6 (PfD6) was collected in Sierra Leone. PfD6 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is generally considered drug sensitive with minor mefloquine resistance. ✖ Parasite growth inhibition assay - - 8.3 pIC50 - 3 ⤷ pIC50 8.3 (IC50 4.6x10-9 M) [3H]-hypoxanthine incorporation [3] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) Unknown MOA PfTM90C2A Plasmodium falciparum TM90C2A P. falciparum TM90C2A (PfTM90C2A) is a clinical isolate, first described during a Phase 2 clinical trial to determine atovaquone efficacy in Thailand (PMID:8651372). PfTM90C2A is sensitive to atovaquone. ✖ Parasite growth inhibition assay - - 8.2 pIC50 - 3 ⤷ pIC50 8.2 (IC50 5.8x10-9 M) [3H]-hypoxanthine incorporation [3] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) Unknown MOA PfK1 Plasmodium falciparum K1 P. falciparum strain K1 (PfK1) was isolated in Kanchanaburi, Thailand in 1979. PfK1 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is reported to be a multidrug-resistant strain. ✖ Parasite growth inhibition assay - - 8.1 pIC50 - 3 ⤷ pIC50 8.1 (IC50 7.7x10-9 M) [3H]-hypoxanthine incorporation [3] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) Unknown MOA PfV1/S Plasmodium falciparum V1/S P. falciparum strain V1/S (PfV1/S) is an in vitro culture-adapted clone of V1, that originated in Vietnam. PfV1/S can be obtained from the Malaria Research and Reference Reagent Resource Center (MR4) and is reported to be resistant to chloroquine and quinine. ✖ Parasite growth inhibition assay - - 8.0 pIC50 - 3 ⤷ pIC50 8.0 (IC50 9.4x10-9 M) [3H]-hypoxanthine incorporation [3] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) Unknown MOA Pf7G8 Plasmodium falciparum 7G8 P. falciparum strain 7G8 (Pf7G8) was subcloned from the IMTM22 strain by limiting dilution. The original IMTM22 strain was isolated from a 12 year old male near Manaus, Brazil in 1980. Pf7G8 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4). This strain is a gametocyte producer and is reported to be chloroquine-sensitive and pyrimethamine-resistant. ✖ Parasite growth inhibition assay - - 8.0 pIC50 - 3 ⤷ pIC50 8.0 (IC50 9.9x10-9 M) [3H]-hypoxanthine incorporation [3] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont) Unknown MOA PfW2 Plasmodium falciparum W2 P. falciparum strain W2 (PfW2) was cloned from the Indochina III/CDC isolate, originally derived from a Laotian patient who failed chloroquine therapy. PfW2 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is reported to be resistant to chloroquine and susceptible to mefloquine. ✖ Parasite growth inhibition assay - - 8.0 pIC50 - 3 ⤷ pIC50 8.0 (IC50 1.08x10-8 M) [3H]-hypoxanthine incorporation [3] Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)

Targets where the ligand is described in the comment field
Target	Comment
CYP2C8	Converts arachidonic acid to 11(R)-12(S)-epoxyeicosatrienoic acid or 14(R)-15(S)-epoxyeicosatrienoic acid [5]. Drug substrates include amodiaquine and paclitaxel [1].