Table 1 Mechanism of action of antiplasmodial natural products

Fatty acid metabolism

Inhibitionof type II fatty acid synthase (FAS II) enzymes

Plasmodium falciparum enoyl-ACP reductase (PfFabI)

Oroidin

Bromopyrrole alkaloid

[290]

Luteolin 7-O-β-d-glucopyranoside

Flavonoid glycoside

[291]

Anthecularin

Sesquiterpene lactone

[292]

4-Hydroxyanthecotulide

Sesquiterpene lactone

[293]

4-Acetoxyanthecotulide

Sesquiterpene lactone

[293]

Mucusisoflavone C

Flavonoid

[294]

3-O-Methylquercetin

Flavonoid

[294]

Isowighteone

Flavonoid

[294]

Evernic acid

Phenolic acid

[295]

Psoromic acid

Phenolic acid

[295]

Methylenebissantin

Flavonoid

[296]

Plasmodium falciparum β-ketoacyl-ACP reductase (PfFabG)

Anthecularin

Sesquiterpene lactone

[292]

4-Hydroxyanthecotulide

Sesquiterpene lactone

[293]

4-Acetoxyanthecotulide

Sesquiterpene lactone

[293]

Psoromic acid

Phenolic acid

[295]

Plasmodium falciparum β-hydroxyacyl-ACP dehydratase (Pf FabZ)

Evernic acid

Phenolic acid

[295]

Vulpic acid

Phenolic acid

[295]

Psoromic acid

Phenolic acid

[295]

Catechin gallate

Catechin

[297]

Bromopyrrolohomoarginin

Bromopyrrole alkaloid

[93]

Detoxification of haem

Inhibition of β-haematin formation

Haem crystallization

Bromophycolide A

Macrocyclic meroditerpene

[262]

Bergenin

Phenolic glycoside

[298]

Fraxetin

Coumarin

[299]

1,3,6-Trihydroxy-2-(3-methyl but-dienyl)-7-methoxy-8-(3- methyl but-2-enyl)xanthen-9-one

Xanthone

[300]

2-(6-O-Benzoyl-β-d-glucopyranosyloxy)-7-(1α, 2α, 6α-trihydroxy-3-oxocyclohex-4-enoyl)-5-hydroxybenzyl alcohol

Phenolic glycoside

[301]

Dimethylisoborreverine

Indole alkaloid

[46]

Nitidine

Benzophenanthridine alkaloid

[62]

Inhibition of β-haematin formation, inhibition of H₂O₂ and glutathione mediated hemin degradation

Axisonitrile-3

Sesquiterpene isonitrile

[154]

Diisocyanoadociane

Diterpene isonitrile

[154]

Inhibition of β-haematin formation, inhibition of H₂O₂ mediated haemin degradation

Catechin-[5,6-e]-4β-(3,4-dihydroxyphenyl) dihydro-2(3H)-pyranone

Phenylpropanoid catechin

[203]

Mururin A

Phenylpropanoid catechin

[203]

Plasmodium falciparum glutathione transferase (PfGST)

JB42C

Sesquiterpene lactone

[302]

Tral-1

Coumarin catechin

[302]

Oxidative stress

Production of ROS and lipid peroxidation product

Trafficking, transmembrane and vesicular transport parasite proteins

Plakortin

Polyketide endoperoxide

[303]

Haemoglobin degradation

Inhibition of food vacuole falcipains

Falcipain 2

2,3,6-Trihydroxy benzoic acid

Phenolic acid

[304]

2,3,6-Trihydroxy methyl benzoate

Phenolic ester

[304]

Symplostatin 4

Depsipeptide

[284]

Falcipain 2′ and 3

Symplostatin 4

Depsipeptide

[284]

Glyoxalase detoxification system

Inhibition of Plasmodium falciparum glyoxalase I (PfGLOI)

(PfGLOI)

Puberulic acid

Tropone

[305]

Hinokitiol

Tropone

[305]

Tropolone

Tropone

[305]

Protein folding

Inhibition of Plasmodium falciparum Hsp70-1 (PfHsp70-1) chaperone function

(PfHsp70-1)

Malonganenone A

Purine alkaloid

[306]

Malonganenone B

Purine alkaloid

[306]

Malonganenone C

Alkaloid

[306]

Lapachol

Naphthoquinone

[306]

Inhibition of chaperone and ATPase functions

PfHsp70-1, PfHsp70-z

Epigallocatechin 3-gallate

Catechin

[205]

Protein degradation

inhibition of Pf20S proteasome

β5 subunit

Carmaphycin B

Tripeptide

[277]

Ca²⁺ metabolism

Inhibition of SERCA-type Ca²⁺-ATPase

PfATP6

Artemisinins

Sesquiterpene endoperoxide

[307]

Protein biosynthesis

Inhibition of cytoplasmic lysyl-tRNA synthetase

Pf lysyl-tRNA synthetase

Cladosporin

Isocoumarin

[308]