Table 12.
The antiparasitic activity of chalcones.
| Compound(s) “Chemical name(s)” | Parasite species | Study model(s) | Results | Inhibition mechanism | Refs. |
|---|---|---|---|---|---|
| “(E)-1-(2-hydroxy-4-methoxyphenyl)-3-(2-methoxyphenyl)prop-2-en-1-one” | Trypanosoma brucei brucei, Trypanosoma congolense, and Leishmania Mexicana | In vitro | EC50: 0.5, 2.5, and 5.2 μg/mL, respectively | N/A | [156] |
| “(E)-1-(3-methoxy-4-((3-methylbut-2-en-1-yl)oxy) phenyl)-3-(3-nitrophenyl)prop-2-en-1-one” “(E)-1-(3-methoxy-4-((3-methylbut-2-en-1-yl)oxy) phenyl)-3-(3-(trifuoromethyl)phenyl)prop-2-en-1-one” “(E)-3-(3-methoxy-4-((3-methylbut-2-en-1-yl)oxy) phenyl)-1-(2-(trifuoromethyl)phenyl)prop-2-en-1-one” |
L. mexicana | In vitro, In silico |
IC50 < 10 μM | Possibly modulates the activity of fumarate reductase by binding to two crucial binding sites for the target with good affinity. | [157] |
| “(E)-3-(2-bromophenyl)-1-(4-(isopropylamino)phenyl)prop2-en-1-one” “(E)-3-(2-bromophenyl)-1-(4-(ethylamino)phenyl)prop-2-en1-one” |
Toxoplasma gondii | In vitro, In vivo |
Significant anti-toxoplasma activity and reduction of biochemical variables as well as liver and spleen indices | Anti-Toxoplasma effects are enhanced by the Michael receptor found in chalcones' molecular skeleton. | [158] |
| Chalcone derivatives with substituents in the A and B rings “1‐(2‐Aminophenyl)‐3‐(3,4,5‐trimethoxyphenyl)prop‐2‐en‐1‐one” “1‐(2‐Aminophenyl)‐3‐(3,5‐dimethoxyphenyl)prop‐2‐en‐1‐one” “1‐(2‐Hydroxyphenyl)‐3‐(3,4,5‐trimethoxyphenyl)prop‐2‐en‐1‐one” |
Leishmania braziliensis, Trypanosoma cruzi, Plasmodium falciparum | In vitro | EC50: 5.7 against L. braziliensis; EC50 against T. cruzi: 8.1 μM; EC50 against P. falciparum: 59.2 μM | The antiparasitic properties were affected by the hydrogen bonds at C-2′ with carbonyl and the electron-donating substituents in ring B. | [153] |
| Chalcone-thiosemicarbazones “(1E,2E)-3-(phenyl)-1-phenylprop-2-en-1-one thiosemicarbazone” “(1E,2E)-3-(40 -chlorophenyl)-1-phenylprop-2-en-1-one thiosemicarbazone” |
Leishmania amazonensis | In vitro | IC50 against intracellular amastigotes: 3.40 μM, IC50 against Promastigotes: 5.22 μM | Anti-leishmanial properties were improved by moieties with electronic withdrawing effects. | [159] |
| “(E)-1-(4-aminophenyl)-3-phenylprop-2-en-1-one (C1)” “(E)-1-(4-aminophenyl)-3-(4-methoxyphenyl)-prop-2-en-1-one (C4)” “(E)-1-(4-aminophenyl)-3-(4ethoxyphenyl)-prop-2-en-1-one (C9)” |
Leishmania major | In silico | Strong interaction of C9 ligand with the Leishmania major receptor, particularly for the Tyr 217, His 219, and Phe 88 residues | N/A | [160] |
| Benzimidazolyl-chalcones “1-(5-chloro-1H-benzo[d]imidazole-2-yl)-3-(2- chlorophenyl)prop-2-en-1-one” | Leishmania donovani | In vitro | IC50: 0.47 μM (most active compound) | The antileishmanial activity could be affected by the C-5 group of benzimidazole, an electron-withdrawing group in the arylpropenone functional group, or the presence of a heterocycle or hydroxyl group in chalcones. | [161] |
| Chalcone-quinoline conjugates “(E)-3-(furan-2-yl)-1-(4-((5-(quinolin-8-yloxy) pentyl)oxy)phenyl)prop-2-en-1-one” | T. cruzi | In silico | Binding energy: 7.2 kcal/mol (most active compound) | Inhibition of cruzipain | [162] |
| Chloride substituted 2-hydroxy-3,4,6-trimethoxyphenylchalcones “(E)-3-(3,4-dimethoxyphenyl)-1-(2-hydroxy-6-methoxyphenyl)prop-2-en-1-one” | T. cruzi | In vitro, in silico | Reduction of the toxicity of chlorine-substituted molecules on host cells; reduction of intracellular amastigotes and infected cells. | Inhibitory effects are associated with a rise in cytoplasmic ROS, mitochondrial malfunction, necrotic events, as well as the activity of TcTR and TcCr enzymes. | [163] |
| Chalcone and its amino analogs | T. vaginalis | In vitro, In vivo | IC50: 29 μM; no toxicity against Galleria mellonella larvae. | ROS accumulation in human neutrophils induced by trophozoites treated with aminochalcone 3. | [164] |
| (E)-1-(2,5-Dimethoxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-one, (E)-(3,4,5-Trimethoxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-one, (E)-1-(3,4,5-Trimethoxyphenyl)-3-(3,4-dimethoxyphenyl)prop-2-en-1-one | P. falciparum | In vitro | Disruption of all parasite membranes, significant drop in ribosome content of trophozoites, and the cessation of schizont development. | The ultrastructural changes suggest multiple mechanisms of action for the activity of chalcone derivatives | [165] |
| Synthetic chalcone CPN2F “(2E)-3-(2-fluorophenyl)-1-(2-hydroxy- 3,4,6-trimethoxyphenyl)prop-2-en-1-one” |
T. cruzi | In vitro, In silico |
A decrease in the metabolism of protozoa in host cells | N/A | [166] |
| Lophirone E analogs “(E)-1-(2,4-Dihydroxyphenyl)-3-(2-(4-hydroxyphenyl)benzofuran-5-yl)prop-2-en-1-one” “(E)-1-(2,4-Dihydroxyphenyl)-3-(2-(4-hydroxyphenyl)-1-methyl-1H-indol-5-yl)prop-2-en-1-one” “(E)-3-(1-Benzyl-2-(4-hydroxyphenyl)-1H-indol-5-yl)-1-(2,4-dihydroxyphenyl)prop-2-en-1-one” |
Leishmania infantum | In vitro | IC50: 15.3, 27.2, and 15.9 μM, | A free OH at C2′ is essential for the activity of the compound. | [170] |
| Benzimidazolylchalcones | L. donovani | In silico, In vitro |
Binding energies (most active compounds): 6.50–6.24 kcal/mol; IC50 (most active compounds): 0.47, 0.50, and 0.53 μM. | electrophilic substituents such as halogens (Cl), nitro, or hydroxyl on the benzimidazolyl-chalcone raises the negativity of the electron affinity of the molecules, boosting their antileishmanial activities. | [171] |
EC50: Half maximal effective concentration, IC50: Half maximal inhibitory concentration.