Synthesis and Characterization of 2-(2′-hydroxy-5′-chlorophenyl)-6-chloro-4(3H)-Quinazolinone-Based Fluorogenic Probes for Cellular Imaging of Monoamine Oxidases
Synthesis and Characterization of 2-(2′-hydroxy-5′-chlorophenyl)-6-chloro-4(3H)-Quinazolinone-Based Fluorogenic Probes for Cellular Imaging of Monoamine Oxidases
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DOI：
10.1002/asia.201000025
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发表时间：
2010-01-01
影响因子：
4.1
通讯作者：
Xing, Bengang
中科院分区：
文献类型：
--
作者：
Aw, Junxin;Shao, Qing;Xing, Bengang
单胺氧化酶（Monoamine oxidases，MAOs）是一种重要的FAD依赖性酶，能有效地催化神经递质和生物胺的氧化脱氨。[1-2]有两种同工型，MAO A和MAO B，在肝脏、胃肠道、血小板和中枢神经系统中丰富。[3]这些酶通过调节胺类神经递质和外周饮食胺类的稳态，在代谢和神经发育中发挥重要作用。这些酶的任何过量或不足都会导致各种神经和精神疾病[4]，如抑郁症，帕金森病和阿尔茨海默病，甚至肿瘤的生长抑制和进展。[5-7]因此，开发合适的MAO底物，可用于在复杂的生物系统中选择性和灵敏地监测酶活性具有重要意义。最近，荧光技术作为简单、有效和强大的工具，在体外和体内实时监测蛋白质和酶活性，引起了相当大的关注[8，9]。[10荧光检测由于其高灵敏度、相对安全、低成本和易于处理而比比色或放射性同位素测定更有利。[12到目前为止，已经成功地采用了几种标准的显色、放射化学和荧光底物来鉴定体外MAO活性。[14-20]然而，仍然高度需要可以提供活细胞中MAO活性的直接和灵敏读出的简单和有效的荧光探针，因为大多数现有方法灵敏度较低，[17-19]需要二级活化酶来释放用于检测的信号[15]或不提供酶的活细胞荧光成像
Monoamine oxidases (MAOs) are essential FAD-dependent enzymes which can efficiently catalyze the oxidative deamination of neurotransmitters and biogenic amines.[1-2] There are two isoforms, MAO A and MAO B, that are abundant in the liver, gastrointestinal tract, blood platelets and central nervous systems.[3] These enzymes play an important role in metabolism and neural development by regulating the homeostasis of amine neurotransmitters and peripheral dietary amines. Any excess or deficiency of these enzymes will lead to various neurological and psychiatric disorders [4] such as depression, Parkinson’s and Alzheimers’s diseases or even the growth inhibition and progression of tumor.[5-7] Thus, the development of suitable MAO substrates which can be used for selective and sensitive monitoring of enzyme activity in a complex biological system is of great significance.Recently, fluorescence techniques have attracted considerable attention as simple, effective and powerful tools [8, 9] for real-time monitoring of protein and enzyme activities in vitro and in vivo.[10, 11] Fluorescent detection is more advantageous compared to colorimetric or radioisotope assay due to its high sensitivity, relative safety, low cost and easy handling.[12, 13] To date, several standard chromogenic, radiochemical and fluorogenic substrates have been successfully employed to identify MAO activity in vitro.[14-20] However, the simple and effective fluorescent probes which can provide a direct and sensitive readout of the MAO activity in living cells is still highly required since most of the existing methods are less sensitive,[17-19] require a secondary activating enzyme to release the signal for detection [15] or do not provide live cell fluorescence imaging for the enzyme