Evaluation of antiplasmodial activity in silico and in vitro of N-acylhydrazone derivatives
Abstract N-acylhydrazones are considered privileged structures in medicinal chemistry, being part of antimicrobial compounds (for example). In this study we show the activity of N-acylhydrazone compounds, namely AH1, AH2, AH4, AH5 in in vitro tests against the chloroquine-resistant strain of Plasmod...
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | BMC Chemistry |
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| Online Access: | https://doi.org/10.1186/s13065-022-00843-9 |
| _version_ | 1818158413117390848 |
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| author | Fernanda A. Oliveira Ana Claudia S. Pinto Caique L. Duarte Alex G. Taranto Eder Lorenzato Junior Cleydson Finotti Cordeiro Diogo T. Carvalho Fernando P. Varotti Amanda L. Fonseca |
| author_facet | Fernanda A. Oliveira Ana Claudia S. Pinto Caique L. Duarte Alex G. Taranto Eder Lorenzato Junior Cleydson Finotti Cordeiro Diogo T. Carvalho Fernando P. Varotti Amanda L. Fonseca |
| author_sort | Fernanda A. Oliveira |
| collection | DOAJ |
| description | Abstract N-acylhydrazones are considered privileged structures in medicinal chemistry, being part of antimicrobial compounds (for example). In this study we show the activity of N-acylhydrazone compounds, namely AH1, AH2, AH4, AH5 in in vitro tests against the chloroquine-resistant strain of Plasmodium falciparum (W2) and against WI26 VA-4 human cell lines. All compounds showed low cytotoxicity (LC50 > 100 µM). The AH5 compound was the most active against Plasmodium falciparum, with an IC50 value of 0.07 μM. AH4 and AH5 were selected among the tested compounds for molecular docking calculations to elucidate possible targets involved in their mechanism of action and the SwissADME analysis to predict their pharmacokinetic profile. The AH5 compound showed affinity for 12 targets with low selectivity, while the AH4 compound had greater affinity for only one target (3PHC). These compounds met Lipinski's standards in the ADME in silico tests, indicating good bioavailability results. These results demonstrate that these N-acylhydrazone compounds are good candidates for future preclinical studies against malaria. Graphical Abstract |
| first_indexed | 2024-12-11T15:29:41Z |
| format | Article |
| id | doaj.art-f3b3899391b14600960590dfc72d872a |
| institution | Directory Open Access Journal |
| issn | 2661-801X |
| language | English |
| last_indexed | 2024-12-11T15:29:41Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Chemistry |
| spelling | doaj.art-f3b3899391b14600960590dfc72d872a2022-12-22T01:00:07ZengBMCBMC Chemistry2661-801X2022-07-0116111310.1186/s13065-022-00843-9Evaluation of antiplasmodial activity in silico and in vitro of N-acylhydrazone derivativesFernanda A. Oliveira0Ana Claudia S. Pinto1Caique L. Duarte2Alex G. Taranto3Eder Lorenzato Junior4Cleydson Finotti Cordeiro5Diogo T. Carvalho6Fernando P. Varotti7Amanda L. Fonseca8Núcleo de Pesquisa Em Química Biológica (NQBio), Universidade Federal de São João Del ReiNúcleo de Pesquisa Em Química Biológica (NQBio), Universidade Federal de São João Del ReiNúcleo de Pesquisa Em Química Biológica (NQBio), Universidade Federal de São João Del ReiNúcleo de Pesquisa Em Química Biológica (NQBio), Universidade Federal de São João Del ReiLaboratório de Pesquisa Em Química Farmacêutica, Universidade Federal de AlfenasLaboratório de Pesquisa Em Química Farmacêutica, Universidade Federal de AlfenasLaboratório de Pesquisa Em Química Farmacêutica, Universidade Federal de AlfenasNúcleo de Pesquisa Em Química Biológica (NQBio), Universidade Federal de São João Del ReiNúcleo de Pesquisa Em Química Biológica (NQBio), Universidade Federal de São João Del ReiAbstract N-acylhydrazones are considered privileged structures in medicinal chemistry, being part of antimicrobial compounds (for example). In this study we show the activity of N-acylhydrazone compounds, namely AH1, AH2, AH4, AH5 in in vitro tests against the chloroquine-resistant strain of Plasmodium falciparum (W2) and against WI26 VA-4 human cell lines. All compounds showed low cytotoxicity (LC50 > 100 µM). The AH5 compound was the most active against Plasmodium falciparum, with an IC50 value of 0.07 μM. AH4 and AH5 were selected among the tested compounds for molecular docking calculations to elucidate possible targets involved in their mechanism of action and the SwissADME analysis to predict their pharmacokinetic profile. The AH5 compound showed affinity for 12 targets with low selectivity, while the AH4 compound had greater affinity for only one target (3PHC). These compounds met Lipinski's standards in the ADME in silico tests, indicating good bioavailability results. These results demonstrate that these N-acylhydrazone compounds are good candidates for future preclinical studies against malaria. Graphical Abstracthttps://doi.org/10.1186/s13065-022-00843-9MalariaBioinformaticsMolecular modeling |
| spellingShingle | Fernanda A. Oliveira Ana Claudia S. Pinto Caique L. Duarte Alex G. Taranto Eder Lorenzato Junior Cleydson Finotti Cordeiro Diogo T. Carvalho Fernando P. Varotti Amanda L. Fonseca Evaluation of antiplasmodial activity in silico and in vitro of N-acylhydrazone derivatives BMC Chemistry Malaria Bioinformatics Molecular modeling |
| title | Evaluation of antiplasmodial activity in silico and in vitro of N-acylhydrazone derivatives |
| title_full | Evaluation of antiplasmodial activity in silico and in vitro of N-acylhydrazone derivatives |
| title_fullStr | Evaluation of antiplasmodial activity in silico and in vitro of N-acylhydrazone derivatives |
| title_full_unstemmed | Evaluation of antiplasmodial activity in silico and in vitro of N-acylhydrazone derivatives |
| title_short | Evaluation of antiplasmodial activity in silico and in vitro of N-acylhydrazone derivatives |
| title_sort | evaluation of antiplasmodial activity in silico and in vitro of n acylhydrazone derivatives |
| topic | Malaria Bioinformatics Molecular modeling |
| url | https://doi.org/10.1186/s13065-022-00843-9 |
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