1. Synthesis and antiproliferative evaluation of novel 3,5,8-trisubstituted coumarins against breast cancer.
- Author
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Salem MG, Alqahtani AM, Mali SN, Alshwyeh HA, Jawarkar RD, Altamimi AS, Alshawwa SZ, Al-Olayan E, Saied EM, and Youssef MF
- Subjects
- Humans, Female, DNA Topoisomerases, Type II metabolism, Structure-Activity Relationship, MCF-7 Cells, Molecular Structure, Cell Line, Tumor, Cell Cycle drug effects, ErbB Receptors metabolism, ErbB Receptors antagonists & inhibitors, Coumarins chemistry, Coumarins pharmacology, Coumarins chemical synthesis, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Breast Neoplasms metabolism, Antineoplastic Agents pharmacology, Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Cell Proliferation drug effects, Apoptosis drug effects, Drug Screening Assays, Antitumor
- Abstract
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.
- Published
- 2024
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