Synthesis, Antioxidant and In-Silico Studies of Potent Urease Inhibitors: N-(4{[(4-Methoxyphenethyl)-(substituted)amino]sulfonyl}phenyl)acetamides
Synthesis, Antioxidant and In-Silico Studies of Potent Urease Inhibitors: N-(4{[(4-Methoxyphenethyl)-(substituted)amino]sulfonyl}phenyl)acetamides
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DOI：
10.1055/a-0654-5074
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发表时间：
2019-02-01
期刊：
影响因子：
2.2
通讯作者：
Hassan, Mubashir
中科院分区：
文献类型：
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作者：
Abbasi, Muhammad Athar;Raza, Hussain;Hassan, Mubashir
本研究合成了一系列新的磺胺类化合物，并研究了它们对DPPH和菜豆尿素酶的抑制作用。电子计算机研究也被用来确定这些分子与酶的活性部位的相互作用。2-(4-甲氧基苯基)-1-乙胺(1)与4-(乙酰氨基)苯磺酰氯(2)在pH为9的碳酸钠水溶液中发生亲核取代反应合成N-(4-甲氧基苯乙基)-1-乙胺(3)，收集的沉淀物洗涤干燥得到母体分子N(4[(4-甲氧基苯乙基)氨基]磺酰}苯基)乙酰胺(3)。然后，以二甲基甲酰胺为溶剂，LiH为活化剂，与不同的烷基/芳基卤化物(4a-m)反应，合成了一系列新的N-(4-{[(4-methoxyphenethyl)-(substituted)amino]sulfonyllphenyl)acetamides(5a-m)。所有化合物均经IR、EI-MS、H-1-核磁共振、C-13-核磁共振和CHN分析数据进行了表征。所有合成的化合物都表现出比标准硫脲更高的尿素酶抑制活性。化合物5f表现出很好的酶抑制活性，相对标准硫脲的IC50值为0.0171+/-0.0070 mU M，IC50值为4.7455+/-0.0546 mU M。分子对接研究表明，配体具有良好的结合能，并结合在Taget蛋白的活性区域内。用计算方法对合成的化合物的化学信息学性质进行了评价，发现合成的化合物大多遵循Lipinski规则。
In this study, a new series of sulfonamides derivatives was synthesized and their inhibitory effects on DPPH and jack bean urease were evaluated. The in silico studies were also applied to ascertain the interactions of these molecules with active site of the enzyme. Synthesis was initiated by the nucleophilic substitution reaction of 2-(4-methoxyphenyl)-1-ethanamine (1) with 4-(acetylamino)benzenesulfonyl chloride (2) in aqueous sodium carbonate at pH 9. Precipitates collected were washed and dried to obtain the parent molecule, N(4{[(4methoxy-phenethyl)amino]sulfonyl} phenyl)acetamide (3). Then, this parent was reacted with different alkyl/aralkyl halides, (4a-m), using dimethylformamide (DMF) as solvent and LiH as an activator to produce a series of new N-(4-{[(4-methoxyphenethyl)-(substituted)amino]sulfonyllphenyl)acetamides (5a-m). All the synthesized compounds were characterized by IR, EI-MS, H-1-NMR, C-13-NMR and CHN analysis data. All of the synthesized compounds showed higher urease inhibitory activity than the standard thiourea. The compound 5f exhibited very excellent enzyme inhibitory activity with IC50 value of 0.0171 +/- 0.0070 mu M relative to standard thiourea having IC50 value of 4.7455 +/- 0.0546 mu M. Molecular docking studies suggested that ligands have good binding energy values and bind within the active region of taget protein. Chemo-informatics properties were evaluated by computational approaches and it was found that synthesized compounds mostly obeyed the Lipinski' rule.