| Autor: |
Salem MG; Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia, 41522, Egypt., Alqahtani AM; Department of Pharmaceutical Sciences, Faculty of Pharmacy, Umm Al-Qura University, Makkah, 21955, Saudi Arabia., Mali SN; School of Pharmacy, DY Patil Deemed to be University Sector 7, Nerul, Navi Mumbai, 400706, India., Alshwyeh HA; Department of Biology, College of Science, Imam Abdulrahman Bin Faisal University, Dammam, 31441, Saudi Arabia.; Basic & Applied Scientific Research Centre, Imam Abdulrahman Bin Faisal University, PO Box 1982, Dammam, 31441, Saudi Arabia., Jawarkar RD; Department of Medicinal Chemistry & Drug Discovery, Dr. Rajendra Gode Institute of Pharmacy, University Mardi Road, Amravati, 444603, India., Altamimi AS; Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, PO Box 173, Alkharj, 11942, Saudi Arabia., Alshawwa SZ; Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, PO Box 84428, Riyadh, 11671, Saudi Arabia., Al-Olayan E; Department of Zoology, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia., Saied EM; Chemistry Department (Biochemistry Division), Faculty of Science, Suez Canal University, Ismailia, 41522, Egypt.; Institute for Chemistry, Humboldt Universität zu Berlin, Brook-Taylor-Str. 2, Berlin, 12489, Germany., Youssef MF; Chemistry Department (Organic Chemistry Division), Faculty of Science, Suez Canal University, Ismailia, 41522, Egypt. |
| Abstrakt: |
Aim: This study focused on designing and synthesizing novel derivatives of 3,5,8-trisubstituted coumarin. Results: The synthesized compounds, particularly compound 5 , exhibited significant cytotoxic effects on MCF-7 cells, surpassing staurosporine, and reduced toxicity toward MCF-10A cells, highlighting potential pharmacological advantages. Further, compound 5 altered the cell cycle and significantly increased apoptosis in MCF-7 cells, involving both early (41.7-fold) and late stages (33-fold), while moderately affecting necrotic signaling. The antitumor activity was linked to a notable reduction (4.78-fold) in topoisomerase IIβ expression. Molecular modeling indicated compound 5 's strong affinity for EGFR, human EGF2 and topoisomerase II proteins. Conclusion: These findings highlight compound 5 as a multifaceted antitumor agent for breast cancer. |
