含咪唑的查耳酮类化合物作为新型单胺氧化酶抑制剂。
Imidazole bearing chalcones as a new class of monoamine oxidase inhibitors.
机构信息
College of Pharmaceutical Science, Government T.D. Medical College, Alappuzha, Kerala, India; Organic Chemistry Division, SAS, VIT University, Vellore, Tamil Nadu, India.
Department of Pharmacy and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Republic of Korea.
出版信息
Biomed Pharmacother. 2018 Oct;106:8-13. doi: 10.1016/j.biopha.2018.06.064. Epub 2018 Jun 23.
In the present study, series of eleven (2E)-1-[4-(1H-imidazol-1-yl)substituted phenyl]-3-phenylprop-2-en-1-one (IM1-IM11) derivatives were synthesized and evaluated as inhibitors of recombinant human monoamine oxidase (MAO) A and B. The results indicate that (2E)-3-[4-(dimethylamino) phenyl]-1-[4-(1H-imidazol-1-yl) phenyl] prop-2-en-1-one (IM5) is a nonselective and reversible competitive inhibitor of MAO-A and MAO-B with IC values of 0.30 ± 0.010 and 0.40 ± 0.017 μM, respectively ; those of (2E)-1-[4-(1H-imidazol-1-yl) phenyl]-3-(4-methylphenyl) prop-2-en-1-one (IM4) were 1.06 ± 0.090 and 0.32 ± 0.021 μM, respectively. Kinetic studies document that both IM5 and IM4 are competitive inhibitors of MAO-A and MAO-B with Ki value of 0.11 ± 0.0085 and 0.085 ± 0.0064 μM, respectively. Molecular docking studies of lead compounds further explained the binding modes in the inhibitor binding cavity of both MAO-A and MAO-B.
在本研究中，合成了一系列十一（2E）-1-[4-（1H-咪唑-1-基）取代苯基]-3-苯基丙-2-烯-1-酮（IM1-IM11）衍生物，并将其作为重组人单胺氧化酶（MAO）A 和 B 的抑制剂进行了评估。结果表明，（2E）-3-[4-（二甲基氨基）苯基]-1-[4-（1H-咪唑-1-基）苯基]丙-2-烯-1-酮（IM5）是非选择性和可逆竞争性 MAO-A 和 MAO-B 的抑制剂，IC 值分别为 0.30±0.010 和 0.40±0.017 μM；（2E）-1-[4-（1H-咪唑-1-基）苯基]-3-（4-甲基苯基）丙-2-烯-1-酮（IM4）的 IC 值分别为 1.06±0.090 和 0.32±0.021 μM。动力学研究表明，IM5 和 IM4 均为 MAO-A 和 MAO-B 的竞争性抑制剂，Ki 值分别为 0.11±0.0085 和 0.085±0.0064 μM。对先导化合物的分子对接研究进一步解释了抑制剂在 MAO-A 和 MAO-B 的抑制剂结合腔中的结合模式。
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