Table 1.
Mechanism of action of antiplasmodial natural products
| Pathway | Mechanism of action | Target | Compound | Compound class | References |
|---|---|---|---|---|---|
| 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] |