Exploring the Anticancer Properties of 1,2,3-Triazole-Substituted Andrographolide Derivatives
<b>Background/Objectives</b>: The search for new anticancer agents from natural sources remains a key strategy in drug discovery. This study aimed to synthesize and evaluate novel triazole derivatives of the diterpenic lactone andrographolide for their antiproliferative activity against...
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MDPI AG
2025-05-01
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| Online Access: | https://www.mdpi.com/1424-8247/18/5/750 |
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| author | Joana R. L. Ribeiro Juliana Calheiros Rita A. M. Silva Bruno M. F. Gonçalves Carlos A. M. Afonso Lucília Saraiva Maria-José U. Ferreira |
| author_facet | Joana R. L. Ribeiro Juliana Calheiros Rita A. M. Silva Bruno M. F. Gonçalves Carlos A. M. Afonso Lucília Saraiva Maria-José U. Ferreira |
| author_sort | Joana R. L. Ribeiro |
| collection | DOAJ |
| description | <b>Background/Objectives</b>: The search for new anticancer agents from natural sources remains a key strategy in drug discovery. This study aimed to synthesize and evaluate novel triazole derivatives of the diterpenic lactone andrographolide for their antiproliferative activity against various cancer cell lines. <b>Methods</b>: Twenty-two new triazole derivatives (<b>5</b>–<b>26</b>), of the triacetyl derivative (<b>2</b>) of the diterpenic lactone andrographolide (<b>1</b>), were synthesized via the azide-alkyne “click reaction”. The antiproliferative effects of compounds <b>1</b>–<b>26</b> were evaluated using the sulforhodamine B assay against a panel of cancer cell lines and a non-tumorigenic colon cell line. A representative compound, triazole derivative <b>12</b>, was further evaluated in human pancreatic ductal adenocarcinoma (PANC-1) cells for its effects on the cell cycle, apoptosis, migration, and drug synergy with 5-fluorouracil. <b>Results</b>: Several compounds, specifically, <b>9</b>, <b>14</b>, <b>16,</b> and <b>17</b>, bearing a phenyl moiety, exhibited improved antiproliferative activity compared to the parental compound <b>1</b>. Derivative <b>12</b>, selected for further investigation, induced G2/M cell cycle arrest and apoptosis in a concentration-dependent manner. Additionally, this compound significantly reduced cell migration and demonstrated synergistic effects with 5-fluorouracil in PANC-1 cells. <b>Conclusions</b>: The synthesized andrographolide-based triazole derivatives, particularly compound <b>12</b>, showed promising antiproliferative activity and mechanisms relevant to cancer therapy. These findings support their potential as lead compounds for further development in anticancer research. |
| format | Article |
| id | doaj-art-ffca8ebe15b94971b1d3ffaae9a2e40d |
| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
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| series | Pharmaceuticals |
| spelling | doaj-art-ffca8ebe15b94971b1d3ffaae9a2e40d2025-08-20T03:47:58ZengMDPI AGPharmaceuticals1424-82472025-05-0118575010.3390/ph18050750Exploring the Anticancer Properties of 1,2,3-Triazole-Substituted Andrographolide DerivativesJoana R. L. Ribeiro0Juliana Calheiros1Rita A. M. Silva2Bruno M. F. Gonçalves3Carlos A. M. Afonso4Lucília Saraiva5Maria-José U. Ferreira6Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, PortugalLAQV/REQUIMTE-Associated Laboratory for Green Chemistry (LAQV) of the Network of Chemistry and Technology (REQUIMTE), Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, Universidade do Porto, 4050-313 Porto, PortugalLAQV/REQUIMTE-Associated Laboratory for Green Chemistry (LAQV) of the Network of Chemistry and Technology (REQUIMTE), Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, Universidade do Porto, 4050-313 Porto, PortugalResearch Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, PortugalResearch Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, PortugalLAQV/REQUIMTE-Associated Laboratory for Green Chemistry (LAQV) of the Network of Chemistry and Technology (REQUIMTE), Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, Universidade do Porto, 4050-313 Porto, PortugalResearch Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal<b>Background/Objectives</b>: The search for new anticancer agents from natural sources remains a key strategy in drug discovery. This study aimed to synthesize and evaluate novel triazole derivatives of the diterpenic lactone andrographolide for their antiproliferative activity against various cancer cell lines. <b>Methods</b>: Twenty-two new triazole derivatives (<b>5</b>–<b>26</b>), of the triacetyl derivative (<b>2</b>) of the diterpenic lactone andrographolide (<b>1</b>), were synthesized via the azide-alkyne “click reaction”. The antiproliferative effects of compounds <b>1</b>–<b>26</b> were evaluated using the sulforhodamine B assay against a panel of cancer cell lines and a non-tumorigenic colon cell line. A representative compound, triazole derivative <b>12</b>, was further evaluated in human pancreatic ductal adenocarcinoma (PANC-1) cells for its effects on the cell cycle, apoptosis, migration, and drug synergy with 5-fluorouracil. <b>Results</b>: Several compounds, specifically, <b>9</b>, <b>14</b>, <b>16,</b> and <b>17</b>, bearing a phenyl moiety, exhibited improved antiproliferative activity compared to the parental compound <b>1</b>. Derivative <b>12</b>, selected for further investigation, induced G2/M cell cycle arrest and apoptosis in a concentration-dependent manner. Additionally, this compound significantly reduced cell migration and demonstrated synergistic effects with 5-fluorouracil in PANC-1 cells. <b>Conclusions</b>: The synthesized andrographolide-based triazole derivatives, particularly compound <b>12</b>, showed promising antiproliferative activity and mechanisms relevant to cancer therapy. These findings support their potential as lead compounds for further development in anticancer research.https://www.mdpi.com/1424-8247/18/5/750andrographolide1,2,3-triazole-substituted derivativesantiproliferativeapoptosiscell cycle arrestantimigratory |
| spellingShingle | Joana R. L. Ribeiro Juliana Calheiros Rita A. M. Silva Bruno M. F. Gonçalves Carlos A. M. Afonso Lucília Saraiva Maria-José U. Ferreira Exploring the Anticancer Properties of 1,2,3-Triazole-Substituted Andrographolide Derivatives Pharmaceuticals andrographolide 1,2,3-triazole-substituted derivatives antiproliferative apoptosis cell cycle arrest antimigratory |
| title | Exploring the Anticancer Properties of 1,2,3-Triazole-Substituted Andrographolide Derivatives |
| title_full | Exploring the Anticancer Properties of 1,2,3-Triazole-Substituted Andrographolide Derivatives |
| title_fullStr | Exploring the Anticancer Properties of 1,2,3-Triazole-Substituted Andrographolide Derivatives |
| title_full_unstemmed | Exploring the Anticancer Properties of 1,2,3-Triazole-Substituted Andrographolide Derivatives |
| title_short | Exploring the Anticancer Properties of 1,2,3-Triazole-Substituted Andrographolide Derivatives |
| title_sort | exploring the anticancer properties of 1 2 3 triazole substituted andrographolide derivatives |
| topic | andrographolide 1,2,3-triazole-substituted derivatives antiproliferative apoptosis cell cycle arrest antimigratory |
| url | https://www.mdpi.com/1424-8247/18/5/750 |
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