Discovery of novel thiazolyl-pyrazolines as dual EGFR and VEGFR-2 inhibitors endowed with in vitro antitumor activity towards non-small lung cancer
New series of thiazolyl-pyrazoline derivatives (7a–7d, 10a–10d and 13a–13f) have been synthesised and assessed for their potential EGFR and VEGFR-2 inhibitory activities. Compounds 10b and 10d exerted potent and selective inhibitory activity towards the two receptor tyrosine kinases; EGFR (IC50 = 40...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2022.2104841 |
| _version_ | 1798036997464391680 |
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| author | Esraa A. Abdelsalam Amer Ali Abd El-Hafeez Wagdy M. Eldehna Mahmoud A. El Hassab Hala Mohamed M. Marzouk Mahmoud M. Elaasser Nageh A. Abou Taleb Kamilia M. Amin Hatem A. Abdel-Aziz Pradipta Ghosh Sherif F. Hammad |
| author_facet | Esraa A. Abdelsalam Amer Ali Abd El-Hafeez Wagdy M. Eldehna Mahmoud A. El Hassab Hala Mohamed M. Marzouk Mahmoud M. Elaasser Nageh A. Abou Taleb Kamilia M. Amin Hatem A. Abdel-Aziz Pradipta Ghosh Sherif F. Hammad |
| author_sort | Esraa A. Abdelsalam |
| collection | DOAJ |
| description | New series of thiazolyl-pyrazoline derivatives (7a–7d, 10a–10d and 13a–13f) have been synthesised and assessed for their potential EGFR and VEGFR-2 inhibitory activities. Compounds 10b and 10d exerted potent and selective inhibitory activity towards the two receptor tyrosine kinases; EGFR (IC50 = 40.7 ± 1.0 and 32.5 ± 2.2 nM, respectively) and VEGFR-2 (IC50 = 78.4 ± 1.5 and 43.0 ± 2.4 nM, respectively). The best anti-proliferative activity for the examined thiazolyl-pyrazolines was observed against the non-small lung cancer cells (NSCLC). Compounds 10b and 10d displayed pronounced efficacy against A549 (IC50 = 4.2 and 2.9 µM, respectively) and H441 cell lines (IC50 = 4.8 and 3.8 µM, respectively). Moreover, our results indicated that 10b and 10d were much more effective towards EGFR-mutated NSCLC cell lines (NCI-H1650 and NCI-H1975 cells) than gefitinib. Finally, compounds 10b and 10d induce G2/M cell cycle arrest and apoptosis and inhibit migration in A549 cancerous cells. |
| first_indexed | 2024-04-11T21:20:39Z |
| format | Article |
| id | doaj.art-b318c71ba4e546f488ee43fd5d801d58 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-04-11T21:20:39Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-b318c71ba4e546f488ee43fd5d801d582022-12-22T04:02:38ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742022-12-013712265228210.1080/14756366.2022.2104841Discovery of novel thiazolyl-pyrazolines as dual EGFR and VEGFR-2 inhibitors endowed with in vitro antitumor activity towards non-small lung cancerEsraa A. Abdelsalam0Amer Ali Abd El-Hafeez1Wagdy M. Eldehna2Mahmoud A. El Hassab3Hala Mohamed M. Marzouk4Mahmoud M. Elaasser5Nageh A. Abou Taleb6Kamilia M. Amin7Hatem A. Abdel-Aziz8Pradipta Ghosh9Sherif F. Hammad10Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Cairo, EgyptDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USADepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, EgyptDepartment of Medicinal Chemistry, Faculty of Pharmacy, King Salman International University (KSIU), South Sinai, EgyptDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USAThe Regional Center for Mycology and Biotechnology, Al-Azhar University, Cairo, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Cairo, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, EgyptDepartment of Applied Organic Chemistry, National Research Centre, Dokki, Giza, EgyptDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USADepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Cairo, EgyptNew series of thiazolyl-pyrazoline derivatives (7a–7d, 10a–10d and 13a–13f) have been synthesised and assessed for their potential EGFR and VEGFR-2 inhibitory activities. Compounds 10b and 10d exerted potent and selective inhibitory activity towards the two receptor tyrosine kinases; EGFR (IC50 = 40.7 ± 1.0 and 32.5 ± 2.2 nM, respectively) and VEGFR-2 (IC50 = 78.4 ± 1.5 and 43.0 ± 2.4 nM, respectively). The best anti-proliferative activity for the examined thiazolyl-pyrazolines was observed against the non-small lung cancer cells (NSCLC). Compounds 10b and 10d displayed pronounced efficacy against A549 (IC50 = 4.2 and 2.9 µM, respectively) and H441 cell lines (IC50 = 4.8 and 3.8 µM, respectively). Moreover, our results indicated that 10b and 10d were much more effective towards EGFR-mutated NSCLC cell lines (NCI-H1650 and NCI-H1975 cells) than gefitinib. Finally, compounds 10b and 10d induce G2/M cell cycle arrest and apoptosis and inhibit migration in A549 cancerous cells.https://www.tandfonline.com/doi/10.1080/14756366.2022.2104841Anticancermolecular dockingEGFR inhibitorsVEGFR-2 inhibitorsEGFR-mutated NSCLCdual kinase inhibitors |
| spellingShingle | Esraa A. Abdelsalam Amer Ali Abd El-Hafeez Wagdy M. Eldehna Mahmoud A. El Hassab Hala Mohamed M. Marzouk Mahmoud M. Elaasser Nageh A. Abou Taleb Kamilia M. Amin Hatem A. Abdel-Aziz Pradipta Ghosh Sherif F. Hammad Discovery of novel thiazolyl-pyrazolines as dual EGFR and VEGFR-2 inhibitors endowed with in vitro antitumor activity towards non-small lung cancer Journal of Enzyme Inhibition and Medicinal Chemistry Anticancer molecular docking EGFR inhibitors VEGFR-2 inhibitors EGFR-mutated NSCLC dual kinase inhibitors |
| title | Discovery of novel thiazolyl-pyrazolines as dual EGFR and VEGFR-2 inhibitors endowed with in vitro antitumor activity towards non-small lung cancer |
| title_full | Discovery of novel thiazolyl-pyrazolines as dual EGFR and VEGFR-2 inhibitors endowed with in vitro antitumor activity towards non-small lung cancer |
| title_fullStr | Discovery of novel thiazolyl-pyrazolines as dual EGFR and VEGFR-2 inhibitors endowed with in vitro antitumor activity towards non-small lung cancer |
| title_full_unstemmed | Discovery of novel thiazolyl-pyrazolines as dual EGFR and VEGFR-2 inhibitors endowed with in vitro antitumor activity towards non-small lung cancer |
| title_short | Discovery of novel thiazolyl-pyrazolines as dual EGFR and VEGFR-2 inhibitors endowed with in vitro antitumor activity towards non-small lung cancer |
| title_sort | discovery of novel thiazolyl pyrazolines as dual egfr and vegfr 2 inhibitors endowed with in vitro antitumor activity towards non small lung cancer |
| topic | Anticancer molecular docking EGFR inhibitors VEGFR-2 inhibitors EGFR-mutated NSCLC dual kinase inhibitors |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2022.2104841 |
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