EGFR tyrosine kinase inhibitor: design, synthesis, characterization, biological evaluation, and molecular docking of novel 1,3,4-oxadiazole, thio-methyl, and 1,2,3-triazole hybrids
Abstract Concerning the structural analysis and optimization of various potential EGFR inhibitors. A series of heterocyclic compounds incorporating pyridine, 1,3,4-oxadiazole, thio-methyl, and 1,2,3-triazole were successfully synthesized via a click reaction 12–21, resulting in high yields. The synt...
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| Format: | Article |
| Language: | English |
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2025-07-01
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| Series: | Journal of Saudi Chemical Society |
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| Online Access: | https://doi.org/10.1007/s44442-025-00004-2 |
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| author | Asma Khalaf Alshamari Aljazi Abdullah AlRashidi Faiza I. A. Abdella Hissah Khashman Alshammari Mona Zaheed Alshammari Nuha Othman S. Alsaif Tamer El Malah |
| author_facet | Asma Khalaf Alshamari Aljazi Abdullah AlRashidi Faiza I. A. Abdella Hissah Khashman Alshammari Mona Zaheed Alshammari Nuha Othman S. Alsaif Tamer El Malah |
| author_sort | Asma Khalaf Alshamari |
| collection | DOAJ |
| description | Abstract Concerning the structural analysis and optimization of various potential EGFR inhibitors. A series of heterocyclic compounds incorporating pyridine, 1,3,4-oxadiazole, thio-methyl, and 1,2,3-triazole were successfully synthesized via a click reaction 12–21, resulting in high yields. The synthesis process entailed the reaction of terminal alkynes, specifically 2-(prop-2-yn-1-ylthio)-5-(pyridin-4-yl)-1,3,4-oxadiazole 1 with various substituted aryl azides 2–11. The cytotoxic properties of the resulting derivatives were assessed against HCT-116, HePG-2, and MCF-7 cancer cell lines. Notably, Compound 19 displayed the highest activity among the tested compounds, with selectivity towards the tumor cells, yielding IC50 values of low micromolar level. Consequently, a series of biological assays were conducted to elucidate the potential mechanism of action of the most potent derivative. Compound 19 demonstrated considerable suppression of EGFR, with an IC50 value of 0.313 µM. This highly effective EGFR inhibitor, Compound 19, halted the HePG-2 cell cycle at the G0/G1 phase by triggering the apoptotic pathway. Moreover, molecular docking illustrated a distinctive interaction of compound 19 with the EGFR binding pocket. This work ultimately presents new derivatives of 1,3,4-oxadiazole, thio-methyl, and 1,2,3-triazole as potential cytotoxic agents and EGFR inhibitors, which should be the subject of further research in tumor therapy. |
| format | Article |
| id | doaj-art-8bc68ef0a56b48d2a4ccbf95c4b7f50e |
| institution | Kabale University |
| issn | 1319-6103 2212-4640 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Springer |
| record_format | Article |
| series | Journal of Saudi Chemical Society |
| spelling | doaj-art-8bc68ef0a56b48d2a4ccbf95c4b7f50e2025-08-20T03:45:39ZengSpringerJournal of Saudi Chemical Society1319-61032212-46402025-07-0129311810.1007/s44442-025-00004-2EGFR tyrosine kinase inhibitor: design, synthesis, characterization, biological evaluation, and molecular docking of novel 1,3,4-oxadiazole, thio-methyl, and 1,2,3-triazole hybridsAsma Khalaf Alshamari0Aljazi Abdullah AlRashidi1Faiza I. A. Abdella2Hissah Khashman Alshammari3Mona Zaheed Alshammari4Nuha Othman S. Alsaif5Tamer El Malah6Department of Chemistry College of Science, Ha’il UniversityDepartment of Chemistry College of Science, Ha’il UniversityDepartment of Chemistry College of Science, Ha’il UniversityDepartment of Chemistry College of Science, Ha’il UniversityDepartment of Chemistry College of Science, Ha’il UniversityDepartment of Chemistry College of Science, Ha’il UniversityPhotochemistry Department, Chemical Industries Research Division, National Research CentreAbstract Concerning the structural analysis and optimization of various potential EGFR inhibitors. A series of heterocyclic compounds incorporating pyridine, 1,3,4-oxadiazole, thio-methyl, and 1,2,3-triazole were successfully synthesized via a click reaction 12–21, resulting in high yields. The synthesis process entailed the reaction of terminal alkynes, specifically 2-(prop-2-yn-1-ylthio)-5-(pyridin-4-yl)-1,3,4-oxadiazole 1 with various substituted aryl azides 2–11. The cytotoxic properties of the resulting derivatives were assessed against HCT-116, HePG-2, and MCF-7 cancer cell lines. Notably, Compound 19 displayed the highest activity among the tested compounds, with selectivity towards the tumor cells, yielding IC50 values of low micromolar level. Consequently, a series of biological assays were conducted to elucidate the potential mechanism of action of the most potent derivative. Compound 19 demonstrated considerable suppression of EGFR, with an IC50 value of 0.313 µM. This highly effective EGFR inhibitor, Compound 19, halted the HePG-2 cell cycle at the G0/G1 phase by triggering the apoptotic pathway. Moreover, molecular docking illustrated a distinctive interaction of compound 19 with the EGFR binding pocket. This work ultimately presents new derivatives of 1,3,4-oxadiazole, thio-methyl, and 1,2,3-triazole as potential cytotoxic agents and EGFR inhibitors, which should be the subject of further research in tumor therapy.https://doi.org/10.1007/s44442-025-00004-2EGFRCancer1,3,4-oxadiazole1,2,3-triazoleApoptosisCell cycle arrest |
| spellingShingle | Asma Khalaf Alshamari Aljazi Abdullah AlRashidi Faiza I. A. Abdella Hissah Khashman Alshammari Mona Zaheed Alshammari Nuha Othman S. Alsaif Tamer El Malah EGFR tyrosine kinase inhibitor: design, synthesis, characterization, biological evaluation, and molecular docking of novel 1,3,4-oxadiazole, thio-methyl, and 1,2,3-triazole hybrids Journal of Saudi Chemical Society EGFR Cancer 1,3,4-oxadiazole 1,2,3-triazole Apoptosis Cell cycle arrest |
| title | EGFR tyrosine kinase inhibitor: design, synthesis, characterization, biological evaluation, and molecular docking of novel 1,3,4-oxadiazole, thio-methyl, and 1,2,3-triazole hybrids |
| title_full | EGFR tyrosine kinase inhibitor: design, synthesis, characterization, biological evaluation, and molecular docking of novel 1,3,4-oxadiazole, thio-methyl, and 1,2,3-triazole hybrids |
| title_fullStr | EGFR tyrosine kinase inhibitor: design, synthesis, characterization, biological evaluation, and molecular docking of novel 1,3,4-oxadiazole, thio-methyl, and 1,2,3-triazole hybrids |
| title_full_unstemmed | EGFR tyrosine kinase inhibitor: design, synthesis, characterization, biological evaluation, and molecular docking of novel 1,3,4-oxadiazole, thio-methyl, and 1,2,3-triazole hybrids |
| title_short | EGFR tyrosine kinase inhibitor: design, synthesis, characterization, biological evaluation, and molecular docking of novel 1,3,4-oxadiazole, thio-methyl, and 1,2,3-triazole hybrids |
| title_sort | egfr tyrosine kinase inhibitor design synthesis characterization biological evaluation and molecular docking of novel 1 3 4 oxadiazole thio methyl and 1 2 3 triazole hybrids |
| topic | EGFR Cancer 1,3,4-oxadiazole 1,2,3-triazole Apoptosis Cell cycle arrest |
| url | https://doi.org/10.1007/s44442-025-00004-2 |
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