New oxadiazole and pyrazoline derivatives as anti-proliferative agents targeting EGFR-TK: design, synthesis, biological evaluation and molecular docking study
Abstract Two new series of oxadiazole and pyrazoline derivatives were designed and synthesized as promising EGFR-TK inhibitors. The in vitro antiproliferative activity was studied against three human cancer cell lines; HCT116, HepG-2 and MCF7 using MTT assay. Compound 10c showed the most potent anti...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-03-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-55046-0 |
| _version_ | 1797266839617667072 |
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| author | Marwa I. Serag Samar S. Tawfik Sahar M. I. Badr Hassan M. Eisa |
| author_facet | Marwa I. Serag Samar S. Tawfik Sahar M. I. Badr Hassan M. Eisa |
| author_sort | Marwa I. Serag |
| collection | DOAJ |
| description | Abstract Two new series of oxadiazole and pyrazoline derivatives were designed and synthesized as promising EGFR-TK inhibitors. The in vitro antiproliferative activity was studied against three human cancer cell lines; HCT116, HepG-2 and MCF7 using MTT assay. Compound 10c showed the most potent anticancer activity against all cancer cell lines, with IC50 range of 1.82 to 5.55 μM, while proving safe towards normal cells WI-38 (IC50 = 41.17 μM) compared to the reference drug doxorubicin (IC50 = 6.72 μM). The most active candidates 5a, 9b, 10a, 10b and 10c were further assessed for their EGFR-TK inhibition. The best of which, compounds 5a and 10b showed IC50 of 0.09 and 0.16 μM respectively compared to gefitinib (IC50 = 0.04 μM). Further investigation against other EGFR family members, showed that 5a displayed good activities against HER3 and HER4 with IC50 values 0.18 and 0.37 µM, respectively compared to gefitinib (IC50 = 0.35 and 0.58 µM, respectively). Furthermore, 5a was evaluated for cell cycle distribution and apoptotic induction on HepG-2 cells. It induced mitochondrial apoptotic pathway and increased accumulation of ROS. Molecular docking study came in agreement with the biological results. Compounds 5a and 10b showed promising drug-likeness with good physicochemical properties. |
| first_indexed | 2024-04-25T01:07:04Z |
| format | Article |
| id | doaj.art-6284f0a0aa3541e7984ea263ae2507cf |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-25T01:07:04Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-6284f0a0aa3541e7984ea263ae2507cf2024-03-10T12:11:08ZengNature PortfolioScientific Reports2045-23222024-03-0114111710.1038/s41598-024-55046-0New oxadiazole and pyrazoline derivatives as anti-proliferative agents targeting EGFR-TK: design, synthesis, biological evaluation and molecular docking studyMarwa I. Serag0Samar S. Tawfik1Sahar M. I. Badr2Hassan M. Eisa3Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura UniversityDepartment of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura UniversityDepartment of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura UniversityDepartment of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura UniversityAbstract Two new series of oxadiazole and pyrazoline derivatives were designed and synthesized as promising EGFR-TK inhibitors. The in vitro antiproliferative activity was studied against three human cancer cell lines; HCT116, HepG-2 and MCF7 using MTT assay. Compound 10c showed the most potent anticancer activity against all cancer cell lines, with IC50 range of 1.82 to 5.55 μM, while proving safe towards normal cells WI-38 (IC50 = 41.17 μM) compared to the reference drug doxorubicin (IC50 = 6.72 μM). The most active candidates 5a, 9b, 10a, 10b and 10c were further assessed for their EGFR-TK inhibition. The best of which, compounds 5a and 10b showed IC50 of 0.09 and 0.16 μM respectively compared to gefitinib (IC50 = 0.04 μM). Further investigation against other EGFR family members, showed that 5a displayed good activities against HER3 and HER4 with IC50 values 0.18 and 0.37 µM, respectively compared to gefitinib (IC50 = 0.35 and 0.58 µM, respectively). Furthermore, 5a was evaluated for cell cycle distribution and apoptotic induction on HepG-2 cells. It induced mitochondrial apoptotic pathway and increased accumulation of ROS. Molecular docking study came in agreement with the biological results. Compounds 5a and 10b showed promising drug-likeness with good physicochemical properties.https://doi.org/10.1038/s41598-024-55046-0OxadiazolePyrazolineAnticancer activityEGFR kinaseDocking studies |
| spellingShingle | Marwa I. Serag Samar S. Tawfik Sahar M. I. Badr Hassan M. Eisa New oxadiazole and pyrazoline derivatives as anti-proliferative agents targeting EGFR-TK: design, synthesis, biological evaluation and molecular docking study Scientific Reports Oxadiazole Pyrazoline Anticancer activity EGFR kinase Docking studies |
| title | New oxadiazole and pyrazoline derivatives as anti-proliferative agents targeting EGFR-TK: design, synthesis, biological evaluation and molecular docking study |
| title_full | New oxadiazole and pyrazoline derivatives as anti-proliferative agents targeting EGFR-TK: design, synthesis, biological evaluation and molecular docking study |
| title_fullStr | New oxadiazole and pyrazoline derivatives as anti-proliferative agents targeting EGFR-TK: design, synthesis, biological evaluation and molecular docking study |
| title_full_unstemmed | New oxadiazole and pyrazoline derivatives as anti-proliferative agents targeting EGFR-TK: design, synthesis, biological evaluation and molecular docking study |
| title_short | New oxadiazole and pyrazoline derivatives as anti-proliferative agents targeting EGFR-TK: design, synthesis, biological evaluation and molecular docking study |
| title_sort | new oxadiazole and pyrazoline derivatives as anti proliferative agents targeting egfr tk design synthesis biological evaluation and molecular docking study |
| topic | Oxadiazole Pyrazoline Anticancer activity EGFR kinase Docking studies |
| url | https://doi.org/10.1038/s41598-024-55046-0 |
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