Carboranyl Analogues of Ketoprofen with Cytostatic Activity against Human Melanoma and Colon Cancer Cell Lines
Carboranyl Analogues of Ketoprofen with Cytostatic Activity against Human Melanoma and Colon Cancer Cell Lines
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DOI：
10.1021/acsomega.9b00412
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发表时间：
2019-05-01
期刊：
影响因子：
4.1
通讯作者：
Hey-Hawkins, Evamarie
中科院分区：
文献类型：
--
作者：
Buzharevski, Antonio;Paskas, Svetlana;Hey-Hawkins, Evamarie
酮洛芬是一种广泛使用的非类固醇抗炎药，也具有抗多种癌症的细胞毒活性。这使得酮洛芬成为开发新的非类固醇抗炎药和细胞毒剂的有吸引力的结构先导。最近，在已有药物的结构中引入碳硼烷作为苯基模拟物已成为药物设计中一种有吸引力的策略。在这里，我们报道了四个新的酮洛芬碳硼烷衍生物的合成和评价，其中两个是具有一氧化氮释放部分的前药酯。其中一种前药酯对黑色素瘤和结肠癌细胞株具有很高的细胞抑制活性。在对氧化应激敏感的细胞系中发现了最显著的活性，这显然是由酮洛芬类似物诱导的。
Ketoprofen is a widely used nonsteroidal anti-inflammatory drug (NSAID) that also exhibits cytotoxic activity against various cancers. This makes ketoprofen an attractive structural lead for the development of new NSAIDs and cytotoxic agents. Recently, the incorporation of carboranes as phenyl mimetics in structures of established drugs has emerged as an attractive strategy in drug design. Herein, we report the synthesis and evaluation of four novel carborane-containing derivatives of ketoprofen, two of which are prodrug esters with an nitric oxide-releasing moiety. One of these prodrug esters exhibited high cytostatic activity against melanoma and colon cancer cell lines. The most pronounced activity was found in cell lines that are sensitive to oxidative stress, which was apparently induced by the ketoprofen analogue.