Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia, 41522, Egypt.
Department of Pharmaceutical Sciences, Faculty of Pharmacy, Umm Al-Qura University, Makkah, 21955, Saudi Arabia.
Future Med Chem. 2024;16(11):1053-1073. doi: 10.4155/fmc-2023-0375. Epub 2024 May 6.
This study focused on designing and synthesizing novel derivatives of 3,5,8-trisubstituted coumarin. The synthesized compounds, particularly compound , exhibited significant cytotoxic effects on MCF-7 cells, surpassing staurosporine, and reduced toxicity toward MCF-10A cells, highlighting potential pharmacological advantages. Further, compound 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 's strong affinity for EGFR, human EGF2 and topoisomerase II proteins. These findings highlight compound as a multifaceted antitumor agent for breast cancer.
本研究专注于设计和合成 3,5,8-三取代香豆素的新型衍生物。所合成的化合物，特别是化合物 ，对 MCF-7 细胞表现出显著的细胞毒性作用，超过了 staurosporine，并且对 MCF-10A 细胞的毒性降低，突出了潜在的药理学优势。此外，化合物 改变了 MCF-7 细胞的细胞周期，并显著增加了细胞凋亡，涉及早期（41.7 倍）和晚期（33 倍），同时适度影响坏死信号。抗肿瘤活性与拓扑异构酶 IIβ表达的显著降低（4.78 倍）有关。分子建模表明化合物 对 EGFR、人 EGF2 和拓扑异构酶 II 蛋白具有很强的亲和力。这些发现突出了化合物 作为一种用于乳腺癌的多效抗肿瘤药物。
