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ToolsSteverding, Dietmar, do Nascimento, Lázaro Gomes, Perez-Castillo, Yunierkis and de Sousa, Damião Pergentino (2022) Gallic acid alkyl esters: Trypanocidal and Leishmanicidal activity, and target identification via modeling studies. Molecules, 27 (18). ISSN 1420-3049
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Abstract
Eight gallic acid alkyl esters (1-8) were synthesized via Fischer esterification and evaluated for their trypanocidal and leishmanicidal activity using bloodstream forms of Trypanosoma brucei and promastigotes of Leishmania major. The general cytotoxicity of the esters was evaluated with human HL-60 cells. The compounds displayed moderate to good trypanocidal but zero to low leish-manicidal activity. Gallic acid esters with alkyl chains of three or four carbon atoms in linear arrangement (propyl (4), butyl (5), and isopentyl (6)) were found to be the most trypanocidal compounds with 50% growth inhibition values of ~3 μM. On the other hand, HL-60 cells were less susceptible to the compounds, thus resulting in moderate selectivity indices (ratio of cytotoxic to trypanocidal activity) of >20 for the esters 4-6. Modeling studies combining molecular docking and molecular dynamics simulations suggest that the trypanocidal mechanism of action of gallic acid alkyl esters could be related to the inhibition of the T. brucei alternative oxidase. This suggestion is supported by the observation that trypanosomes became immobile within minutes when incubated with the esters in the presence of glycerol as the sole substrate. These results indicate that gallic acid alkyl esters are interesting compounds to be considered for further antitrypanosomal drug development.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding: This research was partly funded by the Brazilian Agency Conselho National de Desenvolvimento Científico e Tecnológico (CNPq). |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology |
| Depositing User: | LivePure Connector |
| Date Deposited: | 12 Sep 2022 09:30 |
| Last Modified: | 24 Oct 2022 19:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/88094 |
| DOI: | 10.3390/molecules27185876 |
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