Synthesis and biological evaluation of 2-styrylquinolines as antitumour agents and EGFR kinase inhibitors: molecular docking study
A new series of 4,6-disubstituted 2-(4-(dimethylamino)styryl)quinoline 4a,b–9a,b was synthesized by the reaction of 2-(4-(dimethylamino)styryl)-6-substituted quinoline-4-carboxylic acids 3a,b with thiosemicarbazide, p-hydroxybenzaldehyde, ethylcyanoacetate, and 2,4-pentandione. In addition, the anti...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | http://dx.doi.org/10.1080/14756366.2017.1407926 |
| _version_ | 1818778133425291264 |
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| author | Magda A.-A. El-Sayed Walaa M. El-Husseiny Naglaa I. Abdel-Aziz Adel S. El-Azab Hatem A. Abuelizz Alaa A.-M. Abdel-Aziz |
| author_facet | Magda A.-A. El-Sayed Walaa M. El-Husseiny Naglaa I. Abdel-Aziz Adel S. El-Azab Hatem A. Abuelizz Alaa A.-M. Abdel-Aziz |
| author_sort | Magda A.-A. El-Sayed |
| collection | DOAJ |
| description | A new series of 4,6-disubstituted 2-(4-(dimethylamino)styryl)quinoline 4a,b–9a,b was synthesized by the reaction of 2-(4-(dimethylamino)styryl)-6-substituted quinoline-4-carboxylic acids 3a,b with thiosemicarbazide, p-hydroxybenzaldehyde, ethylcyanoacetate, and 2,4-pentandione. In addition, the antitumour activity of all synthesized compounds 3a,b–9a,b was studied via MTT assay against two cancer cell lines (HepG2 and HCT116). Furthermore, epidermal growth factor receptor (EGFR) inhibition, using the most potent antitumour compounds, 3a, 3b, 4a, 4b, and 8a, was evaluated. The interpretation of the results showed clearly that the derivatives 3a, 4a, and 4b exhibited the highest antitumour activities against the tested cell lines HepG2 and HCT116 with IC50 range of 7.7–14.2 µg/ml, in comparison with the reference drugs 5-fluorouracil (IC50 = 7.9 and 5.3 µg/ml, respectively) and afatinib (IC50 = 5.4 and 11.4 µg/ml, respectively). In vitro EGFR screening showed that compounds 3a, 3b, 4a, 4b, and 8a exhibited moderate inhibition towards EGFR with IC50 values at micromolar levels (IC50 range of 16.01–1.11 µM) compared with the reference drugs sorafenib (IC50 = 1.14 µM) and erlotinib (IC50 = 0.1 µM). Molecular docking was performed to study the mode of interaction of compounds 3a and 4b with EGFR kinase. |
| first_indexed | 2024-12-18T11:39:53Z |
| format | Article |
| id | doaj.art-c21610cab0e24712bbdc93c22001da4c |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-12-18T11:39:53Z |
| publishDate | 2018-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-c21610cab0e24712bbdc93c22001da4c2022-12-21T21:09:27ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742018-01-0133119920910.1080/14756366.2017.14079261407926Synthesis and biological evaluation of 2-styrylquinolines as antitumour agents and EGFR kinase inhibitors: molecular docking studyMagda A.-A. El-Sayed0Walaa M. El-Husseiny1Naglaa I. Abdel-Aziz2Adel S. El-Azab3Hatem A. Abuelizz4Alaa A.-M. Abdel-Aziz5Mansoura UniversityMansoura UniversityMansoura UniversityKing Saud UniversityKing Saud UniversityMansoura UniversityA new series of 4,6-disubstituted 2-(4-(dimethylamino)styryl)quinoline 4a,b–9a,b was synthesized by the reaction of 2-(4-(dimethylamino)styryl)-6-substituted quinoline-4-carboxylic acids 3a,b with thiosemicarbazide, p-hydroxybenzaldehyde, ethylcyanoacetate, and 2,4-pentandione. In addition, the antitumour activity of all synthesized compounds 3a,b–9a,b was studied via MTT assay against two cancer cell lines (HepG2 and HCT116). Furthermore, epidermal growth factor receptor (EGFR) inhibition, using the most potent antitumour compounds, 3a, 3b, 4a, 4b, and 8a, was evaluated. The interpretation of the results showed clearly that the derivatives 3a, 4a, and 4b exhibited the highest antitumour activities against the tested cell lines HepG2 and HCT116 with IC50 range of 7.7–14.2 µg/ml, in comparison with the reference drugs 5-fluorouracil (IC50 = 7.9 and 5.3 µg/ml, respectively) and afatinib (IC50 = 5.4 and 11.4 µg/ml, respectively). In vitro EGFR screening showed that compounds 3a, 3b, 4a, 4b, and 8a exhibited moderate inhibition towards EGFR with IC50 values at micromolar levels (IC50 range of 16.01–1.11 µM) compared with the reference drugs sorafenib (IC50 = 1.14 µM) and erlotinib (IC50 = 0.1 µM). Molecular docking was performed to study the mode of interaction of compounds 3a and 4b with EGFR kinase.http://dx.doi.org/10.1080/14756366.2017.1407926StyrylquinolinethiadiazolesynthesisantitumourEGFR kinase inhibitorsmolecular docking |
| spellingShingle | Magda A.-A. El-Sayed Walaa M. El-Husseiny Naglaa I. Abdel-Aziz Adel S. El-Azab Hatem A. Abuelizz Alaa A.-M. Abdel-Aziz Synthesis and biological evaluation of 2-styrylquinolines as antitumour agents and EGFR kinase inhibitors: molecular docking study Journal of Enzyme Inhibition and Medicinal Chemistry Styrylquinoline thiadiazole synthesis antitumour EGFR kinase inhibitors molecular docking |
| title | Synthesis and biological evaluation of 2-styrylquinolines as antitumour agents and EGFR kinase inhibitors: molecular docking study |
| title_full | Synthesis and biological evaluation of 2-styrylquinolines as antitumour agents and EGFR kinase inhibitors: molecular docking study |
| title_fullStr | Synthesis and biological evaluation of 2-styrylquinolines as antitumour agents and EGFR kinase inhibitors: molecular docking study |
| title_full_unstemmed | Synthesis and biological evaluation of 2-styrylquinolines as antitumour agents and EGFR kinase inhibitors: molecular docking study |
| title_short | Synthesis and biological evaluation of 2-styrylquinolines as antitumour agents and EGFR kinase inhibitors: molecular docking study |
| title_sort | synthesis and biological evaluation of 2 styrylquinolines as antitumour agents and egfr kinase inhibitors molecular docking study |
| topic | Styrylquinoline thiadiazole synthesis antitumour EGFR kinase inhibitors molecular docking |
| url | http://dx.doi.org/10.1080/14756366.2017.1407926 |
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