Coumarin Derivatives Exert Anti-Lung Cancer Activity by Inhibition of Epithelial–Mesenchymal Transition and Migration in A549 Cells
A series of coumarin derivatives and isosteres were synthesized from the reaction of triflic intermediates with phenylboronic acids, terminal alkynes, and organozinc compounds through <i>palladium</i>-catalyzed cross-coupling reactions. The in vitro cytotoxic effect of the compounds was...
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| Format: | Article |
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MDPI AG
2022-01-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/1/104 |
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| author | Rodrigo Santos Aquino de Araújo Julianderson de Oliveira dos Santos Carmo Simone Lara de Omena Silva Camila Radelley Azevedo Costa da Silva Tayhana Priscila Medeiros Souza Natália Barbosa de Mélo Jean-Jacques Bourguignon Martine Schmitt Thiago Mendonça de Aquino Renato Santos Rodarte Ricardo Olímpio de Moura José Maria Barbosa Filho Emiliano Barreto Francisco Jaime Bezerra Mendonça-Junior |
| author_facet | Rodrigo Santos Aquino de Araújo Julianderson de Oliveira dos Santos Carmo Simone Lara de Omena Silva Camila Radelley Azevedo Costa da Silva Tayhana Priscila Medeiros Souza Natália Barbosa de Mélo Jean-Jacques Bourguignon Martine Schmitt Thiago Mendonça de Aquino Renato Santos Rodarte Ricardo Olímpio de Moura José Maria Barbosa Filho Emiliano Barreto Francisco Jaime Bezerra Mendonça-Junior |
| author_sort | Rodrigo Santos Aquino de Araújo |
| collection | DOAJ |
| description | A series of coumarin derivatives and isosteres were synthesized from the reaction of triflic intermediates with phenylboronic acids, terminal alkynes, and organozinc compounds through <i>palladium</i>-catalyzed cross-coupling reactions. The in vitro cytotoxic effect of the compounds was evaluated against two non-small cell lung carcinoma (NSCLC) cell lines (A-549 and H2170) and a normal cell line (NIH-3T3) using cisplatin as a reference drug. Additionally, the effects of the most promising coumarin derivative (<b>9f</b>) in reversing the epithelial-to-mesenchymal transition (EMT) in IL-1β-stimulated A549 cells and in inhibiting the EMT-associated migratory ability in A549 cells were also evaluated. <b>9f</b> had the greatest cytotoxic effect (CC<sub>50</sub> = 7.1 ± 0.8 and 3.3 ± 0.5 μM, respectively against A549 and H2170 cells) and CC<sub>50</sub> value of 25.8 µM for NIH-3T3 cells. <b>9f</b> inhibited the IL-1β-induced EMT in epithelial cells by inhibiting the F-actin reorganization, attenuating changes in the actin cytoskeleton reorganization, and downregulating vimentin in A549 cells stimulated by IL-1β. Treatment of A549 cells with <b>9f</b> at 7 µM for 24 h significantly reduced the migration of IL-1β-stimulated cells, which is a phenomenon confirmed by qualitative assessment of the wound closure. Taken together, our findings suggest that coumarin derivatives, especially compound <b>9f</b>, may become a promising candidate for lung cancer therapy, especially in lung cancer promoted by NSCLC cell lines. |
| first_indexed | 2024-03-10T00:43:57Z |
| format | Article |
| id | doaj.art-3495e3abf91948e2ace37a27b7d62bbc |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T00:43:57Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-3495e3abf91948e2ace37a27b7d62bbc2023-11-23T15:02:08ZengMDPI AGPharmaceuticals1424-82472022-01-0115110410.3390/ph15010104Coumarin Derivatives Exert Anti-Lung Cancer Activity by Inhibition of Epithelial–Mesenchymal Transition and Migration in A549 CellsRodrigo Santos Aquino de Araújo0Julianderson de Oliveira dos Santos Carmo1Simone Lara de Omena Silva2Camila Radelley Azevedo Costa da Silva3Tayhana Priscila Medeiros Souza4Natália Barbosa de Mélo5Jean-Jacques Bourguignon6Martine Schmitt7Thiago Mendonça de Aquino8Renato Santos Rodarte9Ricardo Olímpio de Moura10José Maria Barbosa Filho11Emiliano Barreto12Francisco Jaime Bezerra Mendonça-Junior13Laboratory of Synthesis and Drug Delivery, Department of Biological Sciences, State University of Paraiba, João Pessoa 58429-500, PB, BrazilInstitute of Biological and Health Sciences, Federal University of Alagoas, Maceio 57072-900, AL, BrazilInstitute of Biological and Health Sciences, Federal University of Alagoas, Maceio 57072-900, AL, BrazilInstitute of Biological and Health Sciences, Federal University of Alagoas, Maceio 57072-900, AL, BrazilInstitute of Biological and Health Sciences, Federal University of Alagoas, Maceio 57072-900, AL, BrazilLaboratory of Synthesis and Drug Delivery, Department of Biological Sciences, State University of Paraiba, João Pessoa 58429-500, PB, BrazilLaboratoire d’Innovation Thérapeutique, UMR 7200, Labex Medalis, CNRS, Université de Strasbourg, Faculté de Pharmacie, 74 route du Rhin, BP 60024, 67401 Illkirch, FranceLaboratoire d’Innovation Thérapeutique, UMR 7200, Labex Medalis, CNRS, Université de Strasbourg, Faculté de Pharmacie, 74 route du Rhin, BP 60024, 67401 Illkirch, FranceResearch Group on Therapeutic Strategies—GPET, Institute of Chemistry and Biotechnology, Federal University of Alagoas, Maceio 57072-900, AL, BrazilInstitute of Biological and Health Sciences, Federal University of Alagoas, Maceio 57072-900, AL, BrazilLaboratory of Synthesis and Drug Delivery, Department of Biological Sciences, State University of Paraiba, João Pessoa 58429-500, PB, BrazilPost-Graduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraíba, João Pessoa 58051-900, PB, BrazilInstitute of Biological and Health Sciences, Federal University of Alagoas, Maceio 57072-900, AL, BrazilLaboratory of Synthesis and Drug Delivery, Department of Biological Sciences, State University of Paraiba, João Pessoa 58429-500, PB, BrazilA series of coumarin derivatives and isosteres were synthesized from the reaction of triflic intermediates with phenylboronic acids, terminal alkynes, and organozinc compounds through <i>palladium</i>-catalyzed cross-coupling reactions. The in vitro cytotoxic effect of the compounds was evaluated against two non-small cell lung carcinoma (NSCLC) cell lines (A-549 and H2170) and a normal cell line (NIH-3T3) using cisplatin as a reference drug. Additionally, the effects of the most promising coumarin derivative (<b>9f</b>) in reversing the epithelial-to-mesenchymal transition (EMT) in IL-1β-stimulated A549 cells and in inhibiting the EMT-associated migratory ability in A549 cells were also evaluated. <b>9f</b> had the greatest cytotoxic effect (CC<sub>50</sub> = 7.1 ± 0.8 and 3.3 ± 0.5 μM, respectively against A549 and H2170 cells) and CC<sub>50</sub> value of 25.8 µM for NIH-3T3 cells. <b>9f</b> inhibited the IL-1β-induced EMT in epithelial cells by inhibiting the F-actin reorganization, attenuating changes in the actin cytoskeleton reorganization, and downregulating vimentin in A549 cells stimulated by IL-1β. Treatment of A549 cells with <b>9f</b> at 7 µM for 24 h significantly reduced the migration of IL-1β-stimulated cells, which is a phenomenon confirmed by qualitative assessment of the wound closure. Taken together, our findings suggest that coumarin derivatives, especially compound <b>9f</b>, may become a promising candidate for lung cancer therapy, especially in lung cancer promoted by NSCLC cell lines.https://www.mdpi.com/1424-8247/15/1/104anticancer activitylung cancernon-small-cell lung cancerepithelial–mesenchymal transitionmetastasiscoumarin derivative |
| spellingShingle | Rodrigo Santos Aquino de Araújo Julianderson de Oliveira dos Santos Carmo Simone Lara de Omena Silva Camila Radelley Azevedo Costa da Silva Tayhana Priscila Medeiros Souza Natália Barbosa de Mélo Jean-Jacques Bourguignon Martine Schmitt Thiago Mendonça de Aquino Renato Santos Rodarte Ricardo Olímpio de Moura José Maria Barbosa Filho Emiliano Barreto Francisco Jaime Bezerra Mendonça-Junior Coumarin Derivatives Exert Anti-Lung Cancer Activity by Inhibition of Epithelial–Mesenchymal Transition and Migration in A549 Cells Pharmaceuticals anticancer activity lung cancer non-small-cell lung cancer epithelial–mesenchymal transition metastasis coumarin derivative |
| title | Coumarin Derivatives Exert Anti-Lung Cancer Activity by Inhibition of Epithelial–Mesenchymal Transition and Migration in A549 Cells |
| title_full | Coumarin Derivatives Exert Anti-Lung Cancer Activity by Inhibition of Epithelial–Mesenchymal Transition and Migration in A549 Cells |
| title_fullStr | Coumarin Derivatives Exert Anti-Lung Cancer Activity by Inhibition of Epithelial–Mesenchymal Transition and Migration in A549 Cells |
| title_full_unstemmed | Coumarin Derivatives Exert Anti-Lung Cancer Activity by Inhibition of Epithelial–Mesenchymal Transition and Migration in A549 Cells |
| title_short | Coumarin Derivatives Exert Anti-Lung Cancer Activity by Inhibition of Epithelial–Mesenchymal Transition and Migration in A549 Cells |
| title_sort | coumarin derivatives exert anti lung cancer activity by inhibition of epithelial mesenchymal transition and migration in a549 cells |
| topic | anticancer activity lung cancer non-small-cell lung cancer epithelial–mesenchymal transition metastasis coumarin derivative |
| url | https://www.mdpi.com/1424-8247/15/1/104 |
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