Design,synthesis, and analysis of antiproliferative and apoptosis-inducing activities of nitrile derivatives containing a benzofuran scaffold: EGFR inhibition assay and molecular modelling study |
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| Authors: | Salma Fares Khalid B Selim Fatma E Goda Magda A A El-Sayed Nawaf A AlSaif Mohamed M Hefnawy Alaa A-M Abdel-Aziz Adel S El-Azab |
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| Institution: | aFaculty of Pharmacy, Department of Pharmaceutical Organic Chemistry, Mansoura University, Mansoura, Egypt;bFaculty of Pharmacy, Department of Pharmaceutical Chemistry, Delta University for Science and Technology, Gamasa City, Egypt;cDepartment of Pharmaceutical Chemistry, Horus University, New Dammeitta, Egypt;dDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia |
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| Abstract: | New cyanobenzofurans derivatives 2–12 were synthesised, and their antiproliferative activity was examined compared to doxorubicin and Afatinib (IC50 = 4.17–8.87 and 5.5–11.2 µM, respectively). Compounds 2 and 8 exhibited broad-spectrum activity against HePG2 (IC50 = 16.08–23.67 µM), HCT-116 (IC50 = 8.81–13.85 µM), and MCF-7 (IC50 = 8.36–17.28 µM) cell lines. Compounds 2, 3, 8, 10, and 11 were tested as EGFR-TK inhibitors to demonstrate their possible anti-tumour mechanism compared to gefitinib (IC50 = 0.90 µM). Compounds 2, 3, 10, and 11 displayed significant EGFR TK inhibitory activity with IC50 of 0.81–1.12 µM. Compounds 3 and 11 induced apoptosis at the Pre-G phase and cell cycle arrest at the G2/M phase. They also increased the level of caspase-3 by 5.7- and 7.3-fold, respectively. The molecular docking analysis of compounds 2, 3, 10, and 11 indicated that they could bind to the active site of EGFR TK. |
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| Keywords: | Benzofuran antiproliferative activity EGFR TK cell cycle analysis molecular modelling |
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