Antichagasic evaluation, molecular docking and ADMET properties of the chalcone (2E)-3-(2-fluorophenyl)-1-(2-hydroxy- 3,4,6-trimethoxyphenyl)prop-2-en-1-one against Trypanosoma cruzi

Antiviral and antimicrobial applications of chalcones and their derivatives: From nature to greener synthesis

“…The molecular docking simulations assessed this decrease via the synergistic impact related to benznidazole against key therapeutic targets (cruzipain, trypanothione reductase, and T. cruzi glyceraldehyde-3-phosphate dehydrogenase (TcGAPDH)) in the development cycle of Trypanosoma cruzi . The in silico results demonstrated an association between pharmacokinetic features, e.g., renal uptake and release, which suggests that CPN2F has the potential to be used as an antichagasic medication with minimal organic toxicity [ 166 ]. Chalcone-based compounds with hydroxy and methoxy substitution on the aromatic ring A have been shown to exhibit potential inhibitory effects against leishmania and trypanosome strains [ 167 , 168 ].…”

“… [ 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 IC 50 : 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; IC 50 (most active compounds): 0.47, 0.50, and 0.53 μM.…”

Synthesis of Benzocycloalkanone-Based Michael Acceptors and Biological Activities as Antimalarial and Antitrypanosomal Agents

“…Chalcone compounds have a common chemical scaffold of 1,3-diaryl-2-propen-1one, which exists as trans and cis isomers, with the trans isomer being thermodynamically more stable (Figure 4); it can act as a Michael acceptor and inhibit the active site due to its ability to form covalent bonds in some receptors containing a thiol group, such as cysteine proteases or trypanothione reductase. Reports indicate that the chalcones can exert parasiticide activity through their action on several targets, namely: by inhibition of falcipain-2 [28][29][30], sorbitol-induced hemolysis [31], protein kinases (Pfmrk and PfPK5) [32], topoisomerase-II [33], β-hematin [21,22,34], plasmepsin-II, [35] cruzaine, [36] TcGAPDH, [37,38], and Trypanothione reductase [36][37][38]. As part of our program focused on the discovery of new molecules with potential antiparasitic activity, we have recently designed and synthesized a series of quinolinylbenzocycloalkanones, 4-benzylsulfanyl, and 4-benzylsulfonyl chalcones (Figure 5), where some of them were excellent candidates as antimalarials [21,22,39].…”

“…As part of our program focused on the discovery of new molecules with potential antiparasitic activity, we have recently designed and synthesized a series of quinolinylbenzocycloalkanones, 4-benzylsulfanyl, and 4-benzylsulfonyl chalcones (Figure 5), where some of them were excellent candidates as antimalarials [21,22,39]. Reports indicate that the chalcones can exert parasiticide activity through their action on several targets, namely: by inhibition of falcipain-2 [28][29][30], sorbitol-induced hemolysis [31], protein kinases (Pfmrk and PfPK5) [32], topoisomerase-II [33], β-hematin [21,22,34], plasmepsin-II, [35] cruzaine, [36] TcGAPDH, [37,38], and Trypanothione reductase [36][37][38]. As part of our program focused on the discovery of new molecules with potential antiparasitic activity, we have recently designed and synthesized a series of quinolinylbenzocycloalkanones, 4-benzylsulfanyl, and 4-benzylsulfonyl chalcones (Figure 5), where some of them were excellent candidates as antimalarials [21,22,39].…”

“…Reports indicate that the chalcones can exert parasiticide activity through their action on several targets, namely: by inhibition of falcipain-2 [ 28 , 29 , 30 ], sorbitol-induced hemolysis [ 31 ], protein kinases (Pfmrk and PfPK5) [ 32 ], topoisomerase-II [ 33 ], β-hematin [ 21 , 22 , 34 ], plasmepsin-II, [ 35 ] cruzaine, [ 36 ] TcGAPDH, [ 37 , 38 ], and Trypanothione reductase [ 36 , 37 , 38 ]. As part of our program focused on the discovery of new molecules with potential antiparasitic activity, we have recently designed and synthesized a series of quinolinylbenzocycloalkanones, 4-benzylsulfanyl, and 4-benzylsulfonyl chalcones ( Figure 5 ), where some of them were excellent candidates as antimalarials [ 21 , 22 , 39 ].…”