{"title":"鉴定菊花素衍生物在MCF7细胞中的抗癌潜力:生物学见解和计算机评价。","authors":"Sabahat Abdullah, Asia Naz Awan, Mahwish Akhtar, Kainat Ahmed, Omair Anwar Mohiuddin","doi":"10.1080/17568919.2025.2559569","DOIUrl":null,"url":null,"abstract":"<p><strong>Aim: </strong>To synthesize and evaluate the anticancer potential and mechanism of a naturally occurring compound, chrysin derivatives.</p><p><strong>Materials & methods: </strong>A series of 7-substituted phenyl pyrano derivatives of chrysin (3a-k) were synthesized by Michael-type addition reaction and their structures were elucidated using spectroscopic techniques, such as FT-IR, H<sup>1</sup> NMR, C<sup>13</sup> NMR, and MS. In vitro anticancer and cytotoxicity effects were evaluated using MCF7 and mesenchymal stem cells (MSCs). Apoptosis mechanism was evaluated through the expression of pro- and anti-apoptotic proteins, for instance, Bax, Bcl-2, p53, and p21, and the binding score and stability was computed using AutoDock Vina and GROMACS. In silico ADMET analysis was performed via web-based tools like Swiss ADME, pkCSM, ADMETlab 2.0, PreADMET, ProTox II, and Molinspiration.</p><p><strong>Results: </strong>Structure activity relationship (SAR) analysis revealed that the 4-hydroxy substituted phenyl derivative (3h) is important for anticancer activity. 3 h enhanced the expression of Bax, Bcl-2, and p53 while decreases in the expression of oncogene p21 at 16.5 µM concentration showed superior activity to standard carboplatin and was found safe up to 77.95 μM. All the derivatives displayed favorable pharmacokinetic and drug-like properties.</p><p><strong>Conclusion: </strong>The 4-hydroxy substituted phenyl derivative (3h) spectacled enhanced anticancer and safety profile along with considerable pharmacokinetic parameters.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2315-2331"},"PeriodicalIF":3.4000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490362/pdf/","citationCount":"0","resultStr":"{\"title\":\"Identification of chrysin derivatives anticancer potential in MCF7 cells: biological insights and in silico evaluation.\",\"authors\":\"Sabahat Abdullah, Asia Naz Awan, Mahwish Akhtar, Kainat Ahmed, Omair Anwar Mohiuddin\",\"doi\":\"10.1080/17568919.2025.2559569\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aim: </strong>To synthesize and evaluate the anticancer potential and mechanism of a naturally occurring compound, chrysin derivatives.</p><p><strong>Materials & methods: </strong>A series of 7-substituted phenyl pyrano derivatives of chrysin (3a-k) were synthesized by Michael-type addition reaction and their structures were elucidated using spectroscopic techniques, such as FT-IR, H<sup>1</sup> NMR, C<sup>13</sup> NMR, and MS. In vitro anticancer and cytotoxicity effects were evaluated using MCF7 and mesenchymal stem cells (MSCs). Apoptosis mechanism was evaluated through the expression of pro- and anti-apoptotic proteins, for instance, Bax, Bcl-2, p53, and p21, and the binding score and stability was computed using AutoDock Vina and GROMACS. In silico ADMET analysis was performed via web-based tools like Swiss ADME, pkCSM, ADMETlab 2.0, PreADMET, ProTox II, and Molinspiration.</p><p><strong>Results: </strong>Structure activity relationship (SAR) analysis revealed that the 4-hydroxy substituted phenyl derivative (3h) is important for anticancer activity. 3 h enhanced the expression of Bax, Bcl-2, and p53 while decreases in the expression of oncogene p21 at 16.5 µM concentration showed superior activity to standard carboplatin and was found safe up to 77.95 μM. All the derivatives displayed favorable pharmacokinetic and drug-like properties.</p><p><strong>Conclusion: </strong>The 4-hydroxy substituted phenyl derivative (3h) spectacled enhanced anticancer and safety profile along with considerable pharmacokinetic parameters.</p>\",\"PeriodicalId\":12475,\"journal\":{\"name\":\"Future medicinal chemistry\",\"volume\":\" \",\"pages\":\"2315-2331\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2025-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490362/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Future medicinal chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/17568919.2025.2559569\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/9/17 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Future medicinal chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/17568919.2025.2559569","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/9/17 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Identification of chrysin derivatives anticancer potential in MCF7 cells: biological insights and in silico evaluation.
Aim: To synthesize and evaluate the anticancer potential and mechanism of a naturally occurring compound, chrysin derivatives.
Materials & methods: A series of 7-substituted phenyl pyrano derivatives of chrysin (3a-k) were synthesized by Michael-type addition reaction and their structures were elucidated using spectroscopic techniques, such as FT-IR, H1 NMR, C13 NMR, and MS. In vitro anticancer and cytotoxicity effects were evaluated using MCF7 and mesenchymal stem cells (MSCs). Apoptosis mechanism was evaluated through the expression of pro- and anti-apoptotic proteins, for instance, Bax, Bcl-2, p53, and p21, and the binding score and stability was computed using AutoDock Vina and GROMACS. In silico ADMET analysis was performed via web-based tools like Swiss ADME, pkCSM, ADMETlab 2.0, PreADMET, ProTox II, and Molinspiration.
Results: Structure activity relationship (SAR) analysis revealed that the 4-hydroxy substituted phenyl derivative (3h) is important for anticancer activity. 3 h enhanced the expression of Bax, Bcl-2, and p53 while decreases in the expression of oncogene p21 at 16.5 µM concentration showed superior activity to standard carboplatin and was found safe up to 77.95 μM. All the derivatives displayed favorable pharmacokinetic and drug-like properties.
Conclusion: The 4-hydroxy substituted phenyl derivative (3h) spectacled enhanced anticancer and safety profile along with considerable pharmacokinetic parameters.
期刊介绍:
Future Medicinal Chemistry offers a forum for the rapid publication of original research and critical reviews of the latest milestones in the field. Strong emphasis is placed on ensuring that the journal stimulates awareness of issues that are anticipated to play an increasingly central role in influencing the future direction of pharmaceutical chemistry. Where relevant, contributions are also actively encouraged on areas as diverse as biotechnology, enzymology, green chemistry, genomics, immunology, materials science, neglected diseases and orphan drugs, pharmacogenomics, proteomics and toxicology.