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罗非昔布的碳硼衍生物对人黑色素瘤和结肠癌细胞具有细胞抑制活性。

Carboranyl Derivatives of Rofecoxib with Cytostatic Activity against Human Melanoma and Colon Cancer Cells.

机构信息

Institut für Anorganische Chemie, Universität Leipzig, Johannisallee 29, D-04103, Leipzig, Germany.

Department of Immunology, Institute for Biological Research "Siniša Stanković"- National Institute of the Republic of Serbia", Belgrade University, Belgrade, Serbia.

出版信息

Sci Rep. 2020 Mar 16;10(1):4827. doi: 10.1038/s41598-020-59059-3.

DOI:10.1038/s41598-020-59059-3
PMID:32179835
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7076013/
Abstract

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.

摘要

由于环氧化酶-2（COX-2）参与了致癌过程，因此 COX-2 选择性抑制剂因其潜在的细胞毒性而越来越受到关注。此外，将碳硼烷纳入已确立的抗炎药物的结构中可以提高抑制剂的效力和代谢稳定性。在此，我们报告了罗非昔布的碳硼烷衍生物的合成，这些衍生物在微摩尔范围内表现出显著的细胞毒性或细胞抑制活性，并且对黑色素瘤和结肠癌细胞系具有优异的选择性，而对正常细胞的选择性较低。此外，研究表明，罗非昔布的碳硼烷修饰衍生物表现出不同的作用模式，这取决于细胞类型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4906/7076013/f4287d56f2d8/41598_2020_59059_Fig11_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4906/7076013/8b6dade5079b/41598_2020_59059_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4906/7076013/f11347aa64cd/41598_2020_59059_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4906/7076013/8f82e5c9ef97/41598_2020_59059_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4906/7076013/65e44c83e141/41598_2020_59059_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4906/7076013/aa1c93c87e2c/41598_2020_59059_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4906/7076013/0896c00c9944/41598_2020_59059_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4906/7076013/d5669dcb1264/41598_2020_59059_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4906/7076013/23e5ab52aa9c/41598_2020_59059_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4906/7076013/f4287d56f2d8/41598_2020_59059_Fig11_HTML.jpg

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