Design, synthesis, molecular docking and molecular dynamics studies of some 3-methoxy flavone derivatives as an anti-breast cancer agent
Abstract Objective The present study aimed to synthesize flavone hybrids with 3-methoxy substitution and an N-heterocyclic ring at the 4ʹ position of the flavone B ring and test their effectiveness against cancer. Method Molecular docking of 3-methoxy flavone was studied on ER-α and EGFR. By cyclizi...
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| Format: | Article |
| Language: | English |
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Springer
2025-05-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-02491-6 |
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| author | Bharti S. Fegade Somadatta Y. Chaudhari Rupali V. Likhar Ritesh P. Bhole Pravin S. Uttekar Sandeep S. Pathare Swastika Maitra Daniel Ejim Uti Magdi E. A. Zaki Esther Ugo Alum |
| author_facet | Bharti S. Fegade Somadatta Y. Chaudhari Rupali V. Likhar Ritesh P. Bhole Pravin S. Uttekar Sandeep S. Pathare Swastika Maitra Daniel Ejim Uti Magdi E. A. Zaki Esther Ugo Alum |
| author_sort | Bharti S. Fegade |
| collection | DOAJ |
| description | Abstract Objective The present study aimed to synthesize flavone hybrids with 3-methoxy substitution and an N-heterocyclic ring at the 4ʹ position of the flavone B ring and test their effectiveness against cancer. Method Molecular docking of 3-methoxy flavone was studied on ER-α and EGFR. By cyclizing chalcones, various flavonol derivatives were synthesized and 3-methoxy flavones were produced by flavonol methylation. 3-methoxy flavone derivatives substituted with various heterocyclic rings like morpholine, piperidine, N-methyl piperazine, pyrrolidine, triazole, imidazole, and benzimidazole were synthesized. 1HNMR, 13CNMR, IR, and mass spectra verified all compound’s structures. 3-methoxy flavone derivatives evaluated for their anticancer potential by MTT assay and SRB assay on breast cancer (MCF-7 and MDA-MB-231). The molecular dynamics simulation was also studied for active compounds on the human estrogen receptor alpha and epidermal growth factor receptor. Results 3-methoxy flavone derivatives were successfully synthesized and evaluated by spectroscopic studies. The MTT assay on MCF-7 cell lines revealed significant cytotoxic activity of compounds Ciii and Civ by expressing IC50 values of 13.08 ± 1.80 and 20.3 ± 1.47 µg/ml, respectively. The SRB assay on MDA-MB-231 showed a potent response by compounds Cii, Cv & Cvi with IC50 values of 5.54 ± 1.57, 5.44 ± 1.66 and 8.06 ± 1.83 µg/ml, respectively. Overall results showed the effective substitution of 3-methoxy flavone was N-methyl piperazine and piperidine in all cell lines, while triazole substitution was effective in MDA-MB-231 cells. Molecular dynamics study proved the stability of synthesized compounds’ ligands-protein complexes. The structure–activity relationship of flavone derivatives suggests the electron donating group increases the anticancer activity of derivatives in MDA-MB-231, while the same is not reflected in MCF-7 cell lines. Conclusion This study provides a foundation for designing flavone derivatives with N-heterocyclic ring incorporation as anticancer medicines. |
| format | Article |
| id | doaj-art-e2700c3ca00b42af879b3adaf2f2c8f0 |
| institution | OA Journals |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-e2700c3ca00b42af879b3adaf2f2c8f02025-08-20T02:25:15ZengSpringerDiscover Oncology2730-60112025-05-0116112010.1007/s12672-025-02491-6Design, synthesis, molecular docking and molecular dynamics studies of some 3-methoxy flavone derivatives as an anti-breast cancer agentBharti S. Fegade0Somadatta Y. Chaudhari1Rupali V. Likhar2Ritesh P. Bhole3Pravin S. Uttekar4Sandeep S. Pathare5Swastika Maitra6Daniel Ejim Uti7Magdi E. A. Zaki8Esther Ugo Alum9Department of Pharmaceutical Chemistry, LSHGCT Gahlot Institute of PharmacyDepartment of Pharmaceutical Chemistry, Modern College of PharmacyDepartment of Pharmaceutical Chemistry, LSHGCT Gahlot Institute of PharmacyDepartment of Pharmaceutical Chemistry, Dr. D Y Patil Institute of Pharmaceutical Sciences and Research PimpriDnyan Kala Krida & Krushi Prathishthan’s, Late Laxmibai Phadtare College of PharmacyDepartment of Pharmaceutical Chemistry, Bharati Vidyapeeth (Deemed to Be University), Poona College of PharmacyCenter for Global Health Research, Saveetha Institute of Medical and Technical Sciences, Tamil NaduDepartment of Biochemistry/Research and Publications, Kampala International UniversityDepartment of Chemistry, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU)Department of Biochemistry/Research and Publications, Kampala International UniversityAbstract Objective The present study aimed to synthesize flavone hybrids with 3-methoxy substitution and an N-heterocyclic ring at the 4ʹ position of the flavone B ring and test their effectiveness against cancer. Method Molecular docking of 3-methoxy flavone was studied on ER-α and EGFR. By cyclizing chalcones, various flavonol derivatives were synthesized and 3-methoxy flavones were produced by flavonol methylation. 3-methoxy flavone derivatives substituted with various heterocyclic rings like morpholine, piperidine, N-methyl piperazine, pyrrolidine, triazole, imidazole, and benzimidazole were synthesized. 1HNMR, 13CNMR, IR, and mass spectra verified all compound’s structures. 3-methoxy flavone derivatives evaluated for their anticancer potential by MTT assay and SRB assay on breast cancer (MCF-7 and MDA-MB-231). The molecular dynamics simulation was also studied for active compounds on the human estrogen receptor alpha and epidermal growth factor receptor. Results 3-methoxy flavone derivatives were successfully synthesized and evaluated by spectroscopic studies. The MTT assay on MCF-7 cell lines revealed significant cytotoxic activity of compounds Ciii and Civ by expressing IC50 values of 13.08 ± 1.80 and 20.3 ± 1.47 µg/ml, respectively. The SRB assay on MDA-MB-231 showed a potent response by compounds Cii, Cv & Cvi with IC50 values of 5.54 ± 1.57, 5.44 ± 1.66 and 8.06 ± 1.83 µg/ml, respectively. Overall results showed the effective substitution of 3-methoxy flavone was N-methyl piperazine and piperidine in all cell lines, while triazole substitution was effective in MDA-MB-231 cells. Molecular dynamics study proved the stability of synthesized compounds’ ligands-protein complexes. The structure–activity relationship of flavone derivatives suggests the electron donating group increases the anticancer activity of derivatives in MDA-MB-231, while the same is not reflected in MCF-7 cell lines. Conclusion This study provides a foundation for designing flavone derivatives with N-heterocyclic ring incorporation as anticancer medicines.https://doi.org/10.1007/s12672-025-02491-63-Methoxy flavoneFlavonolBreast cancerMCF-7MDA-MB-231 |
| spellingShingle | Bharti S. Fegade Somadatta Y. Chaudhari Rupali V. Likhar Ritesh P. Bhole Pravin S. Uttekar Sandeep S. Pathare Swastika Maitra Daniel Ejim Uti Magdi E. A. Zaki Esther Ugo Alum Design, synthesis, molecular docking and molecular dynamics studies of some 3-methoxy flavone derivatives as an anti-breast cancer agent Discover Oncology 3-Methoxy flavone Flavonol Breast cancer MCF-7 MDA-MB-231 |
| title | Design, synthesis, molecular docking and molecular dynamics studies of some 3-methoxy flavone derivatives as an anti-breast cancer agent |
| title_full | Design, synthesis, molecular docking and molecular dynamics studies of some 3-methoxy flavone derivatives as an anti-breast cancer agent |
| title_fullStr | Design, synthesis, molecular docking and molecular dynamics studies of some 3-methoxy flavone derivatives as an anti-breast cancer agent |
| title_full_unstemmed | Design, synthesis, molecular docking and molecular dynamics studies of some 3-methoxy flavone derivatives as an anti-breast cancer agent |
| title_short | Design, synthesis, molecular docking and molecular dynamics studies of some 3-methoxy flavone derivatives as an anti-breast cancer agent |
| title_sort | design synthesis molecular docking and molecular dynamics studies of some 3 methoxy flavone derivatives as an anti breast cancer agent |
| topic | 3-Methoxy flavone Flavonol Breast cancer MCF-7 MDA-MB-231 |
| url | https://doi.org/10.1007/s12672-025-02491-6 |
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