Synthesis of novel spirochromane incorporating Schiff's bases, potential antiproliferative activity, and dual EGFR/HER2 inhibition: Cell cycle analysis and in silico study
Spirochromanes incorporating Schiff's bases and semicarbazones 4a-e and 5a-j were synthesizedand analyzed for their potential antiproliferative activity using four human cancer cell lines (MCF-7, HCT-116, PC3, and A549). Compounds 5a, 5b and 5g possessed the highest antiproliferative activity a...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Saudi Pharmaceutical Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1319016423002980 |
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| author | Dina I.A. Othman Abdelrahman Hamdi Walaa M. Elhusseiny Adel S. El-Azab Ahmed H. Bakheit Mohamed Hefnawy Alaa A.-M. Abdel-Aziz |
| author_facet | Dina I.A. Othman Abdelrahman Hamdi Walaa M. Elhusseiny Adel S. El-Azab Ahmed H. Bakheit Mohamed Hefnawy Alaa A.-M. Abdel-Aziz |
| author_sort | Dina I.A. Othman |
| collection | DOAJ |
| description | Spirochromanes incorporating Schiff's bases and semicarbazones 4a-e and 5a-j were synthesizedand analyzed for their potential antiproliferative activity using four human cancer cell lines (MCF-7, HCT-116, PC3, and A549). Compounds 5a, 5b and 5g possessed the highest antiproliferative activity among the tested compounds,with an IC50 range of 1.154–9.09 μM. Compound 5j selectively inhibited the PC3 cell proliferation (IC50 = 5.47 μM). Spirochromanes 5a, 5b and 5g exhibited high inhibitory activity against EGFR (IC50 = 0.116, 0.132, and 0.077 μM, respectively) and HER2 (IC50 = 0.055, 0.210 and 0.085 μM, respectively) compared with the references, erlotinib (IC50 = 0.090 and 0.038 μM, respectively) and gefitinib (IC50 = 0.052 and 0.072 μM, respectively). Cell cycle analysis and apoptosis results showed that compounds 5a, 5b and 5g arrested growth inthe S phase, and the programmed cell death induced by these compounds was an apoptotic mechanism rather than a necrotic pathway. Molecular docking studies of spirochromanes 5a, 5b and 5g to EGFR and HER2 binding sites were performed to explore the orientation mode and interaction. |
| first_indexed | 2024-03-11T11:41:25Z |
| format | Article |
| id | doaj.art-4e5c3903315b4d37ba6fe518806d11e8 |
| institution | Directory Open Access Journal |
| issn | 1319-0164 |
| language | English |
| last_indexed | 2024-03-11T11:41:25Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Saudi Pharmaceutical Journal |
| spelling | doaj.art-4e5c3903315b4d37ba6fe518806d11e82023-11-10T04:16:03ZengElsevierSaudi Pharmaceutical Journal1319-01642023-11-013111101803Synthesis of novel spirochromane incorporating Schiff's bases, potential antiproliferative activity, and dual EGFR/HER2 inhibition: Cell cycle analysis and in silico studyDina I.A. Othman0Abdelrahman Hamdi1Walaa M. Elhusseiny2Adel S. El-Azab3Ahmed H. Bakheit4Mohamed Hefnawy5Alaa A.-M. Abdel-Aziz6Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, EgyptDepartment of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, EgyptDepartment of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, EgyptDepartment of Pharmaceutical Chemistry, College of Pharmacy, P.O. Box 2457, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, P.O. Box 2457, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, P.O. Box 2457, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, P.O. Box 2457, King Saud University, Riyadh 11451, Saudi Arabia; Corresponding author.Spirochromanes incorporating Schiff's bases and semicarbazones 4a-e and 5a-j were synthesizedand analyzed for their potential antiproliferative activity using four human cancer cell lines (MCF-7, HCT-116, PC3, and A549). Compounds 5a, 5b and 5g possessed the highest antiproliferative activity among the tested compounds,with an IC50 range of 1.154–9.09 μM. Compound 5j selectively inhibited the PC3 cell proliferation (IC50 = 5.47 μM). Spirochromanes 5a, 5b and 5g exhibited high inhibitory activity against EGFR (IC50 = 0.116, 0.132, and 0.077 μM, respectively) and HER2 (IC50 = 0.055, 0.210 and 0.085 μM, respectively) compared with the references, erlotinib (IC50 = 0.090 and 0.038 μM, respectively) and gefitinib (IC50 = 0.052 and 0.072 μM, respectively). Cell cycle analysis and apoptosis results showed that compounds 5a, 5b and 5g arrested growth inthe S phase, and the programmed cell death induced by these compounds was an apoptotic mechanism rather than a necrotic pathway. Molecular docking studies of spirochromanes 5a, 5b and 5g to EGFR and HER2 binding sites were performed to explore the orientation mode and interaction.http://www.sciencedirect.com/science/article/pii/S1319016423002980SpirochromaneSchiff's basesSynthesisAntiproliferative activityEnzymatic assayApoptosis |
| spellingShingle | Dina I.A. Othman Abdelrahman Hamdi Walaa M. Elhusseiny Adel S. El-Azab Ahmed H. Bakheit Mohamed Hefnawy Alaa A.-M. Abdel-Aziz Synthesis of novel spirochromane incorporating Schiff's bases, potential antiproliferative activity, and dual EGFR/HER2 inhibition: Cell cycle analysis and in silico study Saudi Pharmaceutical Journal Spirochromane Schiff's bases Synthesis Antiproliferative activity Enzymatic assay Apoptosis |
| title | Synthesis of novel spirochromane incorporating Schiff's bases, potential antiproliferative activity, and dual EGFR/HER2 inhibition: Cell cycle analysis and in silico study |
| title_full | Synthesis of novel spirochromane incorporating Schiff's bases, potential antiproliferative activity, and dual EGFR/HER2 inhibition: Cell cycle analysis and in silico study |
| title_fullStr | Synthesis of novel spirochromane incorporating Schiff's bases, potential antiproliferative activity, and dual EGFR/HER2 inhibition: Cell cycle analysis and in silico study |
| title_full_unstemmed | Synthesis of novel spirochromane incorporating Schiff's bases, potential antiproliferative activity, and dual EGFR/HER2 inhibition: Cell cycle analysis and in silico study |
| title_short | Synthesis of novel spirochromane incorporating Schiff's bases, potential antiproliferative activity, and dual EGFR/HER2 inhibition: Cell cycle analysis and in silico study |
| title_sort | synthesis of novel spirochromane incorporating schiff s bases potential antiproliferative activity and dual egfr her2 inhibition cell cycle analysis and in silico study |
| topic | Spirochromane Schiff's bases Synthesis Antiproliferative activity Enzymatic assay Apoptosis |
| url | http://www.sciencedirect.com/science/article/pii/S1319016423002980 |
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