1,2,3-三唑类抑制剂结构及构效关系研究

A Study on the Structures and Structure-Activity Relationships of 1,2,3-Triazoles Inhibitors

1,2,3-三唑类化合物能够抑制葡萄糖苷酶抑制的活性,是抗癌药物潜在的良好靶点。本文从分子构型特点出发,基于概念密度泛函理论,采用B3LYP/6-311++G方法,计算了一系列1 H-1,2,3-三唑类衍生物的反应性描述指数,包括分子的电离势、亲合势、化学势,绝对硬度、亲电性指数等,分析反应性描述指数发现,当取代基中含有醚键或羰基时,分子的电子亲合势明显变大,芳香性取代基对大多数参数有影响,而饱和直链烷烃取代基的长短主要影响log P值和分子体积的大小。拟合的定量构性关系线性方程表明:目标化合物对α-葡萄糖苷酶的抑制活性主要跟电子亲合势、log P和分子体积V有关,其中log P权重最大;而对自由基的抑制活性主要跟前线轨道能量有关,LUMO轨道贡献占主导地位,降低LUMO轨道的能量可提高抑制剂的反应活性。

1,2,3-triazole derivatives were good targets for potential anti-cancer pharmaceuticals due to their inhibitions to glycosidases.The conceptual density functional theory and the B3LYP/6-11++G method was employed to investigate the reactivity indexes of a series of 1 H-1,2,3-triazole derivatives,including the vertical ionization energy,vertical electronic affinity,chemical potential,molecular hardness,electrophilicity and other molecular description parameters.It is found that when the substituent contains an ether bond or a carbonyl group,the electronic affinity of the molecule was increased distinctly.Most of the parameters were affected by aromatic substituents,while the length of the linear alkane substituent determined the log P values and the molecules’volume.The quantitative structure-property relationship models indicated that the inhibitory activity onα-glucosidase was mainly depended on the electron affinity,log P and molecules’volume,of which log P had the largest weight.The inhibitory activity on free radicals was mainly relied on the frontier orbital energies,and the LUMO orbital energy was the dominant.The energy decrease of the LUMO orbitals can increase the reactivity of the inhibitor.