槲皮素类似物在癌症治疗中的应用新见解。
New insights for the use of quercetin analogs in cancer treatment.
作者信息
Iacopetta Domenico, Grande Fedora, Caruso Anna, Mordocco Roberta Alessandra, Plutino Maria Rosaria, Scrivano Luca, Ceramella Jessica, Muià Noemi, Saturnino Carmela, Puoci Francesco, Rosano Camillo, Sinicropi Maria Stefania
机构信息
Department of Pharmacy, Health & Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Italy.
The Department of ChiBioFarAm, Institute for the Study of Nanostructured Materials, ISMN-CNR, O.U. Palermo, University of Messina, 98166, Messina, Italy.
出版信息
Future Med Chem. 2017 Nov;9(17):2011-2028. doi: 10.4155/fmc-2017-0118. Epub 2017 Oct 27.
AIM
Quercetin (Q1) is a flavonoid widely present in plants and endowed with several pharmacological properties mostly due to its antioxidant potential. Q1 shows anticancer activity and could be useful in cancer prevention. On the other hand, Q1 is poorly soluble in water and unstable in physiological systems, and its bioavailability is very low.
METHODS
A small set of Q1 derivatives (Q2-Q9) has been synthesized following opportunely modified chemical procedures previously reported. Anticancer activity has been evaluated by MTT assay. Human Topoisomerases inhibition has been performed by direct enzymatic assays. Apoptosis has been evaluated by TUNEL assay. ROS production and scavenging activity have been determined by immunofluorescence.
RESULTS
The anticancer profile of a small library of Q1 analogues, in which the OH groups were all or partially replaced with hydrophobic functional groups, has been evaluated. Two of the studied compounds demonstrated an interesting cytotoxic profile in two breast cancer models showing the capability to inhibit human Topoisomerases.
CONCLUSION
The studied compounds represent suitable leads for the development of innovative anticancer drugs. [Formula: see text].
目的
槲皮素（Q1）是一种广泛存在于植物中的黄酮类化合物，因其抗氧化潜力而具有多种药理特性。Q1具有抗癌活性，可能对癌症预防有用。另一方面，Q1在水中溶解度低，在生理系统中不稳定，其生物利用度非常低。
方法
按照先前报道的适当修改后的化学程序合成了一小批Q1衍生物（Q2-Q9）。通过MTT法评估抗癌活性。通过直接酶法测定对人拓扑异构酶的抑制作用。通过TUNEL法评估细胞凋亡。通过免疫荧光测定活性氧的产生和清除活性。
结果
评估了一个Q1类似物小文库的抗癌谱，其中OH基团全部或部分被疏水官能团取代。所研究的两种化合物在两种乳腺癌模型中表现出有趣的细胞毒性谱，显示出抑制人拓扑异构酶的能力。
结论
所研究的化合物是开发创新抗癌药物的合适先导物。[公式：见正文]
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