Department of Chemical Sciences, Tezpur University, Napaam, Tezpur, 784028, Assam, India.
J Mol Model. 2010 Mar;16(3):411-8. doi: 10.1007/s00894-009-0551-9. Epub 2009 Jul 21.
In the present work multiple linear regression analyses were performed to build QSAR models for nucleoside analogous using density functional theory (DFT) and molecular mechanics (MM+) based descriptors in both gas and solvent phases. The QSAR models for 14 carbocyclic analogues of nucleosides against murine leukemia cell line (L1210/0) and human T-lymphocyte cell lines (Molt4/C8 and CEM/0) explain more than 90% of the variances in the activity data along with higher values of [Formula: see text]. The energy of the next lowest unoccupied molecular orbital (E(NL)), electrophilicity (omega) and van der Waals surface area (SA) are the main independent factors contributing to the anticancer activity of nucleoside analogues. Inclusion of solvent medium increases the correlation of each descriptor with activity. Based on the key features responsible for anticancer activity, 10 new compounds with rather high anticancer activity have been theoretically designed. Cytotoxic activities of an additional set of 20 nucleoside analogues were also modeled by the same descriptors and found their predicted values to be in good agreement with the experimental values.
在本工作中，采用密度泛函理论（DFT）和基于分子力学（MM+）的描述符，在气相和溶剂相两种条件下，对核苷类似物进行了多元线性回归分析，以构建定量构效关系（QSAR）模型。针对对鼠白血病细胞系（L1210/0）和人 T 淋巴细胞系（Molt4/C8 和 CEM/0）的 14 种碳环核苷类似物的 QSAR 模型，能够解释活性数据中超过 90%的变异性，同时具有更高的[Formula: see text]值。下一个最低未占据分子轨道（E（NL））的能量、电负性（omega）和范德华表面积（SA）是影响核苷类似物抗癌活性的主要独立因素。溶剂介质的包含增加了每个描述符与活性的相关性。基于对抗癌活性有重要影响的关键特征，理论上设计了 10 种具有较高抗癌活性的新化合物。同样的描述符还对另外一组 20 种核苷类似物的细胞毒性活性进行了建模，并发现其预测值与实验值吻合良好。
