喹唑啉氨基酸衍生物作为单胺氧化酶（MAO）抑制剂的合成与评价
Synthesis and evaluation of quinazoline amino acid derivatives as mono amine oxidase (MAO) inhibitors.
作者信息
Khattab Sherine Nabil, Haiba Nesreen Saied, Asal Ahmed Mosaad, Bekhit Adnan A, Amer Adel, Abdel-Rahman Hamdy M, El-Faham Ayman
机构信息
Department of Chemistry, Faculty of Science, Alexandria University, PO Box 426, Ibrahimia, Alexandria 21321, Egypt.
Department of Physics and Chemistry, Faculty of Education, Alexandria University, Egypt.
出版信息
Bioorg Med Chem. 2015 Jul 1;23(13):3574-85. doi: 10.1016/j.bmc.2015.04.021. Epub 2015 Apr 16.
A series of quinazolinone amino acid ester and quinazolinone amino acid hydrazides were prepared under microwave irradiation as well as conventional condition. The microwave irradiation afforded the product in less reaction time, higher yield and purity. The structures of the synthesized compounds were confirmed by IR, NMR, and elemental analysis. The new synthesized compounds were studied for their monoamine oxidase inhibitory activity. They showed more selective inhibitory activity toward MAO-A than MAO-B. Compounds 7, 10, and 15 showed MAO-A inhibition activity (IC50=3.6×10(-9), 2.8×10(-9), 2.1×10(-9) M, respectively) comparable to that of the standard clorgyline (IC50=2.9×10(-9)M). 2-(2-(Benzo[d][1,3]dioxol-5-yl)-4-oxo-1,2-dihydroquinazolin-3(4H)-yl)acetohydrazide 15 showed selective MAO-A inhibition activity (SI=39524) superior to that of the standard clorgyline (SI=33793). The acute toxicity of the synthesized compounds was determined. In addition, computer-assisted simulated docking experiments were performed to rationalize the biological activity.
在微波辐射以及常规条件下制备了一系列喹唑啉酮氨基酸酯和喹唑啉酮氨基酸酰肼。微波辐射使产物的反应时间更短、产率和纯度更高。通过红外光谱（IR）、核磁共振（NMR）和元素分析确定了合成化合物的结构。对新合成的化合物进行了单胺氧化酶抑制活性研究。它们对单胺氧化酶A（MAO-A）的抑制活性比对单胺氧化酶B（MAO-B）更具选择性。化合物7、10和15表现出的MAO-A抑制活性（IC50分别为3.6×10⁻⁹、2.8×10⁻⁹、2.1×10⁻⁹ M）与标准药物氯吉兰（IC50 = 2.9×10⁻⁹ M）相当。2-(2-(苯并[d][1,3]二氧杂环戊烯-5-基)-4-氧代-1,2-二氢喹唑啉-3(4H)-基)乙酰肼15表现出的选择性MAO-A抑制活性（SI = 39524）优于标准药物氯吉兰（SI = 33793）。测定了合成化合物的急性毒性。此外，还进行了计算机辅助模拟对接实验以阐明其生物活性。
Zotero 插件