基于蒙特卡罗方法的作为非核苷类逆转录酶抑制剂的HEPT衍生物的定量构效关系模型。

QSAR models for HEPT derivates as NNRTI inhibitors based on Monte Carlo method.

作者信息

Toropova Alla P, Toropov Andrey A, Veselinović Jovana B, Miljković Filip N, Veselinović Aleksandar M

机构信息

IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.

University of Niš, Faculty of Medicine, Department of Chemistry, Bulevar Dr Zorana Djindjića 81, 18000 Niš, Serbia.

出版信息

Eur J Med Chem. 2014 Apr 22;77:298-305. doi: 10.1016/j.ejmech.2014.03.013. Epub 2014 Mar 11.

DOI:10.1016/j.ejmech.2014.03.013

PMID:24657566

Abstract

A series of 107 1-[(2-hydroxyethoxy)-methyl]-6-(phenylthio) thymine (HEPT) with anti-HIV-1 activity as a non-nucleoside reverse transcriptase inhibitor (NNRTI) has been studied. Monte Carlo method has been used as a tool to build up the quantitative structure-activity relationships (QSAR) for anti-HIV-1 activity. The QSAR models were calculated with the representation of the molecular structure by simplified molecular input-line entry system and by the molecular graph. Three various splits into training and test set were examined. Statistical quality of all build models is very good. Best calculated model had following statistical parameters: for training set r(2) = 0.8818, q(2) = 0.8774 and r(2) = 0.9360, q(2) = 0.9243 for test set. Structural indicators (alerts) for increase and decrease of the IC50 are defined. Using defined structural alerts computer aided design of new potential anti-HIV-1 HEPT derivates is presented.

摘要

对一系列作为非核苷类逆转录酶抑制剂（NNRTI）具有抗HIV-1活性的107种1-[(2-羟基乙氧基)-甲基]-6-(苯硫基)胸腺嘧啶（HEPT）进行了研究。蒙特卡罗方法已被用作建立抗HIV-1活性定量构效关系（QSAR）的工具。QSAR模型是通过简化分子输入线输入系统和分子图来表示分子结构进行计算的。研究了三种不同的训练集和测试集划分。所有建立模型的统计质量都非常好。最佳计算模型具有以下统计参数：训练集的r(2)=0.8818，q(2)=0.8774，测试集的r(2)=0.9360，q(2)=0.9243。定义了IC50增加和减少的结构指标（警示）。利用定义的结构警示，提出了新型潜在抗HIV-1 HEPT衍生物的计算机辅助设计。