Novel 2-substituted-quinoxaline analogs with potential antiproliferative activity against breast cancer: insights into cell cycle arrest, topoisomerase II, and EGFR activity
Manar G. Salem, Sara A. Abu El-ata, Elsherbiny H. El‐Sayed, Suraj N. Mali, Hussah Abdullah Alshwyeh, Ghassan Almaimani, Riyad A. Almaimani, Hussain A. Almasmoum, Najla Altwaijry, Ebtesam Al‐Olayan, Essa M. Saied, Mohamed F. Youssef
Abstract
= 33.7 ± 2.04 μM). Mechanistic studies revealed that compound 3b induced cell cycle arrest at the G1 transition and triggered apoptosis in MCF-7 cells, as evidenced by increasing the percentage of cells arrested in the G2/M and pre-G1 phases utilizing flow cytometric analysis and Annexin V-FITC/PI analysis. Moreover, compound 3b was found to substantially suppress topoisomerase enzyme activity in MCF-7 cells. Molecular modeling studies further supported the potential of compound 3b as a therapeutic candidate by demonstrating significant binding affinity to the active sites of both topoisomerase II and EGFR proteins. Taken together, the presented 2-substituted-quinoxaline analogues, especially compound 3b, show promise as potential candidates for the development of effective anti-breast cancer drugs.