Carboranyl Derivatives of Rofecoxib with Cytostatic Activity against Human Melanoma and Colon Cancer Cells
Carboranyl Derivatives of Rofecoxib with Cytostatic Activity against Human Melanoma and Colon Cancer Cells
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DOI：
10.1038/s41598-020-59059-3
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发表时间：
2020-03-16
影响因子：
4.6
通讯作者：
Hey-Hawkins, Evamarie
中科院分区：
文献类型：
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作者：
Buzharevski, Antonio;Paskas, Svetlana;Hey-Hawkins, Evamarie
由于环氧合酶-2（考克斯-2）参与肿瘤的发生，考克斯-2选择性抑制剂因其潜在的细胞毒性而受到越来越多的研究。此外，在已建立的抗炎药物的结构中掺入碳硼烷可以改善抑制剂的效力和代谢稳定性。在此，我们报告了合成的罗非昔布的含碳硼烷衍生物，其在微摩尔范围内显示出显着的细胞毒性或细胞抑制活性，对黑色素瘤和结肠癌细胞系的选择性优于正常细胞。此外，研究表明，罗非昔布的碳硼烷修饰衍生物显示出依赖于细胞类型的不同作用模式。
Owing to the involvement of cyclooxygenase-2 (COX-2) in carcinogenesis, COX-2-selective inhibitors are increasingly studied for their potential cytotoxic properties. Moreover, the incorporation of carboranes in structures of established anti-inflammatory drugs can improve the potency and metabolic stability of the inhibitors. Herein, we report the synthesis of carborane-containing derivatives of rofecoxib that display remarkable cytotoxic or cytostatic activity in the micromolar range with excellent selectivity for melanoma and colon cancer cell lines over normal cells. Furthermore, it was shown that the carborane-modified derivatives of rofecoxib showed different modes of action that were dependent on the cell type.