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Probing cytochrome P450 bioactivation and fluorescent properties with morpholinyl-tethered anthraquinones
Bioorganic & Medicinal Chemistry Letters ( IF 2.7 ) Pub Date : 2018-03-16 , DOI: 10.1016/j.bmcl.2018.03.040
Rachel J. Errington , Maria Sadiq , Laura Cosentino , Marie Wiltshire , Omair Sadiq , Marcella Sini , Enric Lizano , Maria D. Pujol , Goreti R. Morais , Klaus Pors

Structural features from the anticancer prodrug nemorubicin (MMDX) and the DNA-binding molecule DRAQ5™ were used to prepare anthraquinone-based compounds, which were assessed for their potential to interrogate cytochrome P450 (CYP) functional activity and localisation. 1,4-disubstituted anthraquinone 8 was shown to be 5-fold more potent in EJ138 bladder cancer cells after CYP1A2 bioactivation. In contrast, 1,5-bis((2-morpholinoethyl)amino) substituted anthraquinone 10 was not CYP-bioactivated but was shown to be fluorescent and subsequently photo-activated by a light pulse (at a bandwidth 532–587 nm), resulting in punctuated foci accumulation in the cytoplasm. It also showed low toxicity in human osteosarcoma cells. These combined properties provide an interesting prospective approach for opto-tagging single or a sub-population of cells and seeking their location without the need for continuous monitoring.



中文翻译:

用吗啉基连接的蒽醌探测细胞色素P450的生物活化和荧光性质

使用抗癌前药新霉素(MMDX)和DNA结合分子DRAQ5™的结构特征来制备基于蒽醌的化合物,并评估其对细胞色素P450(CYP)功能活性和定位的潜力。CYP1A2生物激活后,EJ138膀胱癌细胞中1,4-二取代蒽醌8的效力提高了5倍。相比之下,1,5-((2-吗啉代乙基)氨基)取代的蒽醌10并不是通过CYP生物激活的,而是显示为荧光的,随后被光脉冲(在532-587 nm的带宽内)光激活,从而导致在细胞质中聚集了点状的病灶。在人骨肉瘤细胞中也显示出低毒性。这些组合的特性提供了一种有趣的前瞻性方法,可以对单个或部分细胞进行光标记,而无需进行连续监控即可寻找它们的位置。

更新日期:2018-03-16
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