School of Chemical Engineering, Northwest University/Shaanxi Key Laboratory of Physico-Inorganic Chemistry, Xi'an, 710069, P. R. China.
Baoji Hospital of Traditional Chinese Medicine, Baoji, 721000, P. R. China.
Chem Biodivers. 2021 Feb;18(2):e2000804. doi: 10.1002/cbdv.202000804. Epub 2021 Jan 14.
A series of (E)-1-(substituted benzylidene)-4-(3-isopropylphenyl)thiosemicarbazone derivatives were synthesized and characterized by FT-IR spectrum, elemental analysis, NMR spectrum, HR-MS spectrum, and X-ray single crystal diffraction technology. The crystal structures and packing of (E)-1-(4-fluorobenzylidene)-4-(3-isopropylphenyl)thiosemicarbazone and (E)-1-(3-fluorobenzylidene)-4-(3-isopropylphenyl)thiosemicarbazone were maintained through the intramolecular hydrogen bond (N3-H6⋅⋅⋅N1) and intermolecular hydrogen bonds (N2-H4⋅⋅⋅S1, C14-H14⋅⋅⋅F1 and C7-H7⋅⋅⋅S1). The results obtained by employing the DPPH free radicals scavenging assay indicated that (E)-1-(4-methoxylbenzylidene)-4-(3-isopropylphenyl)thiosemicarbazone had a more significant antioxidant activity compared with other compounds. The results measured by adopting the disc diffusion method elucidated that (E)-1-(4-trifluoromethylbenzylidene)-4-(3-isopropylphenyl)thiosemicarbazone possessed a more prominent antifungal activity than other compounds. Molecular docking showed that (E)-1-(4-chlorobenzylidene)-4-(3-isopropylphenyl)thiosemicarbazone had the highest affinity with receptor protein (1NMT). Moreover, the drug-likeness characteristic, physicochemical properties, pharmacokinetic profiles, and bioactivity scores of all the compounds were predicted through in silico studies. The results illustrated that (E)-1-(4-fluorobenzylidene)-4-(3-isopropylphenyl)thiosemicarbazone had the drug-likeness characteristic and all the compounds were considered as moderately biological active molecules.
一系列（E）-1-（取代苄叉基）-4-（3-异丙基苯基）硫代缩氨基脲衍生物通过傅里叶变换红外光谱、元素分析、核磁共振谱、高分辨率质谱和 X 射线单晶衍射技术进行了合成和表征。（E）-1-（4-氟亚苄基）-4-（3-异丙基苯基）硫代缩氨基脲和（E）-1-（3-氟亚苄基）-4-（3-异丙基苯基）硫代缩氨基脲的晶体结构和堆积方式通过分子内氢键（N3-H6⋅⋅⋅N1）和分子间氢键（N2-H4⋅⋅⋅S1、C14-H14⋅⋅⋅F1 和 C7-H7⋅⋅⋅S1）得以维持。采用 DPPH 自由基清除试验得到的结果表明，（E）-1-（4-甲氧基亚苄基）-4-（3-异丙基苯基）硫代缩氨基脲具有比其他化合物更强的抗氧化活性。采用圆盘扩散法得到的结果表明，（E）-1-（4-三氟甲基亚苄基）-4-（3-异丙基苯基）硫代缩氨基脲具有比其他化合物更强的抗真菌活性。分子对接表明，（E）-1-（4-氯亚苄基）-4-（3-异丙基苯基）硫代缩氨基脲与受体蛋白（1NMT）具有最高的亲和力。此外，通过计算机模拟研究预测了所有化合物的药物特性、物理化学性质、药代动力学特征和生物活性评分。结果表明，（E）-1-（4-氟亚苄基）-4-（3-异丙基苯基）硫代缩氨基脲具有药物特性，所有化合物都被认为是具有中等生物活性的分子。
