Integrated in silico and in vitro exploration of the anti-VEGFR-2 activities of a semisynthetic xanthine alkaloid inhibiting breast cancer.
This study presents T-1-NBAB, a new compound derived from the natural xanthine alkaloid theobromine, aimed at inhibiting VEGFR-2, a crucial protein in angiogenesis. T-1-NBAB's potential to interacts with and inhibit the VEGFR-2 was indicated using in silico techniques like molecular docking, MD...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0316146 |
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| author | Eslam B Elkaeed Hazem Elkady Ahmed M Khattab Reda G Yousef Hanan A Al-Ghulikah Dalal Z Husein Ibrahim M Ibrahim Mohamed A Elkady Ahmed M Metwaly Ibrahim H Eissa |
| author_facet | Eslam B Elkaeed Hazem Elkady Ahmed M Khattab Reda G Yousef Hanan A Al-Ghulikah Dalal Z Husein Ibrahim M Ibrahim Mohamed A Elkady Ahmed M Metwaly Ibrahim H Eissa |
| author_sort | Eslam B Elkaeed |
| collection | DOAJ |
| description | This study presents T-1-NBAB, a new compound derived from the natural xanthine alkaloid theobromine, aimed at inhibiting VEGFR-2, a crucial protein in angiogenesis. T-1-NBAB's potential to interacts with and inhibit the VEGFR-2 was indicated using in silico techniques like molecular docking, MD simulations, MM-GBSA, PLIP, essential dynamics, and bi-dimensional projection experiments. DFT experiments was utilized also to study the structural and electrostatic properties of T-1-NBAB. Computational analysis was performed to predict the ADME-Tox profiles of T-1-NBAB. After semisynthesis, the in vitro results showed that T-1-NBAB effectively inhibits VEGFR-2, with an IC50 of 0.115 μM, compared to sorafenib's 0.0591 μM. In vitro tests also demonstrated significant activity of T-1-NBAB against breast cancer cell lines MCF7 and T47D, with IC50 values of 16.88 μM and 61.17 μM, respectively, and high selectivity. Importantly, T-1-NBAB induced early and late apoptosis in MCF7 cells, indicating its potential as a strong anticancer agent. Additionally, T-1-NBAB reduced the migration and healing abilities of MCF7 cells, suggesting it could be a promising anti-angiogenic agent. Overall, these findings suggest that T-1-NBAB is a promising lead compound for further research as a potential treatment for breast cancer. |
| format | Article |
| id | doaj-art-3fdf02d263b044b399bd623df3f50f3c |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-3fdf02d263b044b399bd623df3f50f3c2025-02-05T05:32:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01201e031614610.1371/journal.pone.0316146Integrated in silico and in vitro exploration of the anti-VEGFR-2 activities of a semisynthetic xanthine alkaloid inhibiting breast cancer.Eslam B ElkaeedHazem ElkadyAhmed M KhattabReda G YousefHanan A Al-GhulikahDalal Z HuseinIbrahim M IbrahimMohamed A ElkadyAhmed M MetwalyIbrahim H EissaThis study presents T-1-NBAB, a new compound derived from the natural xanthine alkaloid theobromine, aimed at inhibiting VEGFR-2, a crucial protein in angiogenesis. T-1-NBAB's potential to interacts with and inhibit the VEGFR-2 was indicated using in silico techniques like molecular docking, MD simulations, MM-GBSA, PLIP, essential dynamics, and bi-dimensional projection experiments. DFT experiments was utilized also to study the structural and electrostatic properties of T-1-NBAB. Computational analysis was performed to predict the ADME-Tox profiles of T-1-NBAB. After semisynthesis, the in vitro results showed that T-1-NBAB effectively inhibits VEGFR-2, with an IC50 of 0.115 μM, compared to sorafenib's 0.0591 μM. In vitro tests also demonstrated significant activity of T-1-NBAB against breast cancer cell lines MCF7 and T47D, with IC50 values of 16.88 μM and 61.17 μM, respectively, and high selectivity. Importantly, T-1-NBAB induced early and late apoptosis in MCF7 cells, indicating its potential as a strong anticancer agent. Additionally, T-1-NBAB reduced the migration and healing abilities of MCF7 cells, suggesting it could be a promising anti-angiogenic agent. Overall, these findings suggest that T-1-NBAB is a promising lead compound for further research as a potential treatment for breast cancer.https://doi.org/10.1371/journal.pone.0316146 |
| spellingShingle | Eslam B Elkaeed Hazem Elkady Ahmed M Khattab Reda G Yousef Hanan A Al-Ghulikah Dalal Z Husein Ibrahim M Ibrahim Mohamed A Elkady Ahmed M Metwaly Ibrahim H Eissa Integrated in silico and in vitro exploration of the anti-VEGFR-2 activities of a semisynthetic xanthine alkaloid inhibiting breast cancer. PLoS ONE |
| title | Integrated in silico and in vitro exploration of the anti-VEGFR-2 activities of a semisynthetic xanthine alkaloid inhibiting breast cancer. |
| title_full | Integrated in silico and in vitro exploration of the anti-VEGFR-2 activities of a semisynthetic xanthine alkaloid inhibiting breast cancer. |
| title_fullStr | Integrated in silico and in vitro exploration of the anti-VEGFR-2 activities of a semisynthetic xanthine alkaloid inhibiting breast cancer. |
| title_full_unstemmed | Integrated in silico and in vitro exploration of the anti-VEGFR-2 activities of a semisynthetic xanthine alkaloid inhibiting breast cancer. |
| title_short | Integrated in silico and in vitro exploration of the anti-VEGFR-2 activities of a semisynthetic xanthine alkaloid inhibiting breast cancer. |
| title_sort | integrated in silico and in vitro exploration of the anti vegfr 2 activities of a semisynthetic xanthine alkaloid inhibiting breast cancer |
| url | https://doi.org/10.1371/journal.pone.0316146 |
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