通过对3,5-二芳基-4,5-二氢异恶唑进行支架修饰：新型高效且选择性的单胺氧化酶B抑制剂
Through scaffold modification to 3,5-diaryl-4,5-dihydroisoxazoles: new potent and selective inhibitors of monoamine oxidase B.
作者信息
Meleddu Rita, Distinto Simona, Cirilli Roberto, Alcaro Stefano, Yanez Matilde, Sanna Maria Luisa, Corona Angela, Melis Claudia, Bianco Giulia, Matyus Peter, Cottiglia Filippo, Maccioni Elias
机构信息
a Department of Life and Environmental Sciences , University of Cagliari , Cagliari , Italy.
b Dipartimento del Farmaco , Istituto Superiore di Sanità , Rome , Italy.
出版信息
J Enzyme Inhib Med Chem. 2017 Dec;32(1):264-270. doi: 10.1080/14756366.2016.1247061.
3,5-Diaryl-4,5-dihydroisoxazoles were synthesized and evaluated as monoamine oxidase (MAO) enzyme inhibitors and iron chelators. All compounds exhibited selective inhibitory activity towards the B isoform of MAO in the nanomolar concentration range. The best performing compound was preliminarily evaluated for its ability to bind iron II and III cations, indicating that neither iron II nor iron III is coordinated. The best compounds racemic mixtures were separated and single enantiomers inhibitory activity evaluated. Furthermore, none of the synthesised compounds exhibited activity towards MAO A. Overall, these data support our hypothesis that 3,5-diaryl-4,5-dihydroisoxazoles are promising scaffolds for the design of neuroprotective agents.
合成了3,5 - 二芳基 - 4,5 - 二氢异恶唑，并将其作为单胺氧化酶（MAO）抑制剂和铁螯合剂进行评估。所有化合物在纳摩尔浓度范围内对MAO的B亚型均表现出选择性抑制活性。对表现最佳的化合物初步评估了其与铁II和铁III阳离子结合的能力，结果表明铁II和铁III均未配位。对最佳化合物的外消旋混合物进行了拆分，并评估了单一对映体的抑制活性。此外，合成的化合物均未表现出对MAO A的活性。总体而言，这些数据支持了我们的假设，即3,5 - 二芳基 - 4,5 - 二氢异恶唑是设计神经保护剂的有前景的骨架。
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