摘要
目的:为了研究HEPT 类似物的电子结构与其抗HIV 活性的关系。方法:应用分子力学MM+方法,半经验量子化学MNDO 法计算了23个HEPT 类似物的优势构象和电子结构,结合数理方法得到了两个定量构效方程:(1)log1/C=5.138+0.00005823I_(C-C)+0.00004894E_e+3.747Q_(13);(2)ClogP=5.271+0.0001363I_(C-C)+0.0001134E_e-10.86Q_(S13);结果:(1)HEPT 类似物的两个苯环作为两个核的核与核之间相互作用I_(C-C)和分子总电子能E_e 是影响其log1/C 与ClogP 的主要因素,核与核之间的相互作用越强,总电子能越高,则其疏水参数和其抗HIV 活性也越强。(2)13号原子上取代基的净电荷Q_(S13)越大时,ClogP 越小。当13号原子的净电荷Q_(13)越多,其抗HIV 活性则越强。结论:HEPT 类似物的抗HIV 活性与化合物的核与核之间相互作用、总电子能及13号位的原子的净电荷成正比。
Objective:To analyze the QSAR of 23 HEPT Inhibitors.Methods:the MM+ geometry optimization and MNDO quantumchemical indexes had been performed.The significant QSAR equations can be obtained as below:(1)ClogP=5.271+1.363×10^(-4)I(c.c)+1.134×10^(-4)E_c-10.86Q_(s13);(2)1ogl/C=5.138+5.823×10^(-5)I(c-c)+4.894×10^(-5)E_e+3.747Q_(13);Results:(1)The I_(c-c)and E_e of HEPT derivatives are main factors that affect activity(logl/C)and hydrophobicity(ClogP)of their derivatives.The activi-ties and hydrophobicity of HEPT derivatives will increase with the more values of I_(c-c) and Ee of molecules.(2)ClogP of the derivativewill be less while the net charge Q_(S13) of 13-substituted group of molecule is more;logl/C of the derivative will increase while the netcharge Q_(13) of 13-atom of molecule is more.Conclusions:the anti-HIV activities of HEPT derivatives are increased with increasing ofI_(c.c),E_e,Q_(13) of compound molecules.
出处
《计算机与应用化学》
CAS
CSCD
北大核心
2004年第5期665-668,共4页
Computers and Applied Chemistry
基金
国家重点基础研究"973"项目(G1998051201)
广东省科技攻关基金项目(2KB01202S)
