Facile Synthesis of Some Coumarin Derivatives and Their Cytotoxicity through VEGFR2 and Topoisomerase II Inhibition
Novel semisynthetic coumarin derivatives were synthesized to be developed as chemotherapeutic anticancer agents through topoisomerase II, VEGFR2 inhibition that leads to apoptotic cancer cell death. The coumarin amino acids and dipeptides derivatives were prepared by the reaction of coumarin-3-carbo...
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MDPI AG
2022-11-01
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| author | Mohamed S. Gomaa Ibrahim A. I. Ali Gaber El Enany El Sayed H. El Ashry Samir M. El Rayes Walid Fathalla Abdulghany H. A. Ahmed Samar A. Abubshait Haya A. Abubshait Mohamed S. Nafie |
| author_facet | Mohamed S. Gomaa Ibrahim A. I. Ali Gaber El Enany El Sayed H. El Ashry Samir M. El Rayes Walid Fathalla Abdulghany H. A. Ahmed Samar A. Abubshait Haya A. Abubshait Mohamed S. Nafie |
| author_sort | Mohamed S. Gomaa |
| collection | DOAJ |
| description | Novel semisynthetic coumarin derivatives were synthesized to be developed as chemotherapeutic anticancer agents through topoisomerase II, VEGFR2 inhibition that leads to apoptotic cancer cell death. The coumarin amino acids and dipeptides derivatives were prepared by the reaction of coumarin-3-carboxylic acid with amino acid methyl esters following the <i>N</i>,<i>N</i>-dicyclohexylcarbodiimide (DCC) method and 1-hydroxy-benzotriazole (HOBt), as coupling reagents. The synthesized compounds were screened towards VEGFR2, and topoisomerase IIα proteins to highlight their binding affinities and virtual mechanism of binding. Interestingly, compounds <b>4k</b> (Tyr) and <b>6c</b> (β-Ala-L-Met) shared the activity towards the three proteins by forming the same interactions with the key amino acids, such as the co-crystallized ligands. Both compounds <b>4k</b> and <b>6c</b> exhibited potent cytotoxic activities against MCF-7 cells with IC<sub>50</sub> values of 4.98 and 5.85 µM, respectively causing cell death by 97.82 and 97.35%, respectively. Validating the molecular docking studies, both compounds demonstrated promising VEGFR-2 inhibition with IC<sub>50</sub> values of 23.6 and 34.2 µM, compared to Sorafenib (30 µM) and topoisomerase-II inhibition with IC<sub>50</sub> values of 4.1 and 8.6 µM compared to Doxorubicin (9.65 µM). Hence, these two promising compounds could be further tested as effective and selective target-oriented active agents against cancer. |
| first_indexed | 2024-03-09T17:39:31Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T17:39:31Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj.art-4bafda49c16445d199e59889300a3cc92023-11-24T11:39:38ZengMDPI AGMolecules1420-30492022-11-012723827910.3390/molecules27238279Facile Synthesis of Some Coumarin Derivatives and Their Cytotoxicity through VEGFR2 and Topoisomerase II InhibitionMohamed S. Gomaa0Ibrahim A. I. Ali1Gaber El Enany2El Sayed H. El Ashry3Samir M. El Rayes4Walid Fathalla5Abdulghany H. A. Ahmed6Samar A. Abubshait7Haya A. Abubshait8Mohamed S. Nafie9Department of Pharmaceutical Chemistry, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Suez Canal University, Ismailia 41522, EgyptDepartment of Physics, College of Science and Arts in Uglat Asugour, Qassim University, Buraidah 52571, Saudi ArabiaChemistry Department, Faculty of Science, University of Alexandria, Alexandria 21526, EgyptDepartment of Chemistry, Faculty of Science, Suez Canal University, Ismailia 41522, EgyptScientific Department, Faculty of Engineering, Port Said University, Port Said 42526, EgyptChemistry Department, Faculty of Medicinal Science, University of Science and Technology, Aden 15201, YemenChemistry Department, College of Science, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi ArabiaBasic Science Department, Deanship of Preparatory Year and Supporting Studies, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Suez Canal University, Ismailia 41522, EgyptNovel semisynthetic coumarin derivatives were synthesized to be developed as chemotherapeutic anticancer agents through topoisomerase II, VEGFR2 inhibition that leads to apoptotic cancer cell death. The coumarin amino acids and dipeptides derivatives were prepared by the reaction of coumarin-3-carboxylic acid with amino acid methyl esters following the <i>N</i>,<i>N</i>-dicyclohexylcarbodiimide (DCC) method and 1-hydroxy-benzotriazole (HOBt), as coupling reagents. The synthesized compounds were screened towards VEGFR2, and topoisomerase IIα proteins to highlight their binding affinities and virtual mechanism of binding. Interestingly, compounds <b>4k</b> (Tyr) and <b>6c</b> (β-Ala-L-Met) shared the activity towards the three proteins by forming the same interactions with the key amino acids, such as the co-crystallized ligands. Both compounds <b>4k</b> and <b>6c</b> exhibited potent cytotoxic activities against MCF-7 cells with IC<sub>50</sub> values of 4.98 and 5.85 µM, respectively causing cell death by 97.82 and 97.35%, respectively. Validating the molecular docking studies, both compounds demonstrated promising VEGFR-2 inhibition with IC<sub>50</sub> values of 23.6 and 34.2 µM, compared to Sorafenib (30 µM) and topoisomerase-II inhibition with IC<sub>50</sub> values of 4.1 and 8.6 µM compared to Doxorubicin (9.65 µM). Hence, these two promising compounds could be further tested as effective and selective target-oriented active agents against cancer.https://www.mdpi.com/1420-3049/27/23/8279amino acidscoumarinDCC couplingdipeptidesVEGFR2topoisomerase II |
| spellingShingle | Mohamed S. Gomaa Ibrahim A. I. Ali Gaber El Enany El Sayed H. El Ashry Samir M. El Rayes Walid Fathalla Abdulghany H. A. Ahmed Samar A. Abubshait Haya A. Abubshait Mohamed S. Nafie Facile Synthesis of Some Coumarin Derivatives and Their Cytotoxicity through VEGFR2 and Topoisomerase II Inhibition Molecules amino acids coumarin DCC coupling dipeptides VEGFR2 topoisomerase II |
| title | Facile Synthesis of Some Coumarin Derivatives and Their Cytotoxicity through VEGFR2 and Topoisomerase II Inhibition |
| title_full | Facile Synthesis of Some Coumarin Derivatives and Their Cytotoxicity through VEGFR2 and Topoisomerase II Inhibition |
| title_fullStr | Facile Synthesis of Some Coumarin Derivatives and Their Cytotoxicity through VEGFR2 and Topoisomerase II Inhibition |
| title_full_unstemmed | Facile Synthesis of Some Coumarin Derivatives and Their Cytotoxicity through VEGFR2 and Topoisomerase II Inhibition |
| title_short | Facile Synthesis of Some Coumarin Derivatives and Their Cytotoxicity through VEGFR2 and Topoisomerase II Inhibition |
| title_sort | facile synthesis of some coumarin derivatives and their cytotoxicity through vegfr2 and topoisomerase ii inhibition |
| topic | amino acids coumarin DCC coupling dipeptides VEGFR2 topoisomerase II |
| url | https://www.mdpi.com/1420-3049/27/23/8279 |
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