Coumaro-chalcones synthesized under solvent-free conditions as potential agents against malaria, leishmania and trypanosomiasis

Cuellar, José E.; Quiñones, Winston; Robledo, Sara M.; Gil, José; Durango, Diego

doi:10.1016/j.heliyon.2022.e08939

Cited by 8 publications

(5 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies with chalcone derivatives reveal that the anti-promastigote action of these substances may be related to the formation of pores in the parasite cell membrane, as well as alterations in the membranes involving cellular structures, such as mitochondria, and damage to the parasites' DNA [28][29][30]. These results suggest that these mechanisms may be potentially responsible for the action of the chalcones tested in this study, and still need to be investigated for the molecules of the present work.…”

Section: Discussionmentioning

confidence: 76%

“…A possible explanation for the significant increase in the mean effective concentration for the anti-amastigote action of chalcones is that these molecules have greater specificity for elements present in the promastigote membranes. Furthermore, an increase in the cytotoxic concentration of chalcones in the presence of the amastigote form is common [21,[28][29][30]32]. In these cases, the cytotoxic activity of the compounds may be due to the immunomodulation of infected macrophages by the intracellular form of the parasite, which induces an increase in the production of nitric oxide (NO) and reactive oxygen species (ROS), having direct action on the parasite [21,29].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

In Vitro and In Silico Evaluation of the Anti-leishmanial Activity of Novel Synthetic Chalcones

Leite,

Rodrigues,

De Oliveira

et al. 2023

Preprint

View full text Add to dashboard Cite

Leishmaniasis is a group of neglected infectious, non-contagious diseases caused by parasites of the Leishmania genus which affects millions of people worldwide. The drugs available for its treatment, especially in cases of visceral leishmaniasis, are old, outdated, have serious side effects and in many cases are ineffective due to the emergence of resistant strains. In this context, the search for new candidates for more effective and safer drugs which can become new therapeutic alternatives is a constant need. In this work, 10 new chalcones were synthesized in high yields through Claisen-Schmidt condensation and were evaluated in vitro against Leishmania infantum promastigotes and amastigotes. CP04 and CP06 compounds were the most promising, respectively showing IC50 values = 13.64 ± 0.25 and 11.19 ± 0.22 against promastigotes, and IC50 = 18.92 ± 0.05 and 22.42 ± 0.05 against amastigotes. The compounds did not show cytotoxicity in erythrocytes, showing selectivity indexes greater than 74 and 90. Molecular docking studies carried out under the sterol 14-alpha demethylase (CYP-51) (PDB: 3L4D) and trypanothione reductase (PDB: 5EBK) enzymes from L. infantum evidenced the great affinity of the CP04 molecule for these targets, showing Moldock score values of -94.0758 and -50.5692 KJ/mol-1, with these values being much lower than the co-crystallized ligand energies. Molecular dynamics simulations demonstrated great stability of CP04 in its targets, thus indicating a real interaction possibility. Our findings confirm the potential that chalcones have as candidates for anti-leishmania drugs, and suggest that the CP04 compound may become a promising drug candidate to design and develop novel chalcone-based analogs for leishmaniosis therapy.

show abstract

Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

In Vitro and In Silico Evaluation of the Anti-leishmanial Activity of Novel Synthetic Chalcones

Leite,

Rodrigues,

De Oliveira

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…La concentración efectiva del medio se definió como la concentración del compuesto que disminuye en un 50% los parásitos intracelulares. Los compuestos con EC50 25 μM se consideraron altamente activos Cuellar, et al, 2022.…”

Section: Evaluación De La Actividad Antimalárica (O Anti-plasmodial) ...unclassified

Actividad antiprotozoaria y antioxidante in vitro de extractos y metabolitos mayoritarios aislados de Pilocarpus alvaradoi (Rutaceae)

Marin,

Espinosa,

Guzman

et al. 2024

Inf. tecnol.

View full text Add to dashboard Cite

Esta investigación evalua la actividad antiprotozoaria y antioxidante de extractos etanólicos de hojas y corteza de la especie Pilocarpus alvaradoi. La actividad antioxidante se mide usando los métodos DPPH•, ABTS•+ y FRAP. La actividad antiprotozoaria in vitro es medida frente a los parásitos de Leishmania (V.) panamensis, Tripanosoma cruzi y Plasmodium falciparum. La citotoxicidad se examina frente a células U937. Los compuestos se identifican mediante espectroscopia de RMN. Como resultado se identifican tres compuestos: sesamina, escopoletina y bergapteno. Los extractos etanólicos y subextracto en acetato de etilo de corteza muestran actividad antioxidante de 13.5 y 19.5 mg/L (ABTS•+), 17.4 y 21.1 mg/L (DPPH•) y 52.0 y 51.5 mg/L (FRAP) respectivamente. El extracto etanólico de corteza presenta moderada actividad leishmanicida, antiplásmodial y tripanocida con valores de CE50 de 47.90, 28.05 y 49.06 µg/mL, respectivamente. En conclusión, las sustancias obtenidas de P. alvaradoi se reportan por primera vez para esta especie.

show abstract

“…The aim of the research group of Cuellar and co-workers was to synthesize active pharmacological coumaro-chalcone compounds by a sustainable route (Figure 2B). They applied a classic Claisen-Schmidt condensation without solvent, obtaining high yields (75.2-99.4%) with the selective formation of the trans isomer in the chalconoid system (Cuellar et al, 2022). Exploiting the mechanochemistry technique, another research group performed reactions using nitrones as a replacement for Frontiers in Chemistry frontiersin.org aldehydes.…”

Section: Green Solvents For the Synthesis And Derivatization Of Chalc...mentioning

confidence: 99%

The green chemistry of chalcones: Valuable sources of privileged core structures for drug discovery

Marotta

Rossi²,

Ibba³

et al. 2022

Front. Chem.

View full text Add to dashboard Cite

The sustainable use of resources is essential in all production areas, including pharmaceuticals. However, the aspect of sustainability needs to be taken into consideration not only in the production phase, but during the whole medicinal chemistry drug discovery trajectory. The continuous progress in the fields of green chemistry and the use of artificial intelligence are contributing to the speed and effectiveness of a more sustainable drug discovery pipeline. In this light, here we review the most recent sustainable and green synthetic approaches used for the preparation and derivatization of chalcones, an important class of privileged structures and building blocks used for the preparation of new biologically active compounds with a broad spectrum of potential therapeutic applications. The literature here reported has been retrieved from the SciFinder database using the term “chalcone” as a keyword and filtering the results applying the concept: “green chemistry”, and from the Reaxys database using the keywords “chalcone” and “green”. For both databases the time-frame was 2017–2022. References were manually selected based on relevance.

show abstract

Coumaro-chalcones synthesized under solvent-free conditions as potential agents against malaria, leishmania and trypanosomiasis

Cited by 8 publications

References 23 publications

In Vitro and In Silico Evaluation of the Anti-leishmanial Activity of Novel Synthetic Chalcones

In Vitro and In Silico Evaluation of the Anti-leishmanial Activity of Novel Synthetic Chalcones

Actividad antiprotozoaria y antioxidante in vitro de extractos y metabolitos mayoritarios aislados de Pilocarpus alvaradoi (Rutaceae)

The green chemistry of chalcones: Valuable sources of privileged core structures for drug discovery

Contact Info

Product

Resources

About