Quantitative Structure-Cytotoxicity Relationships of Sesquiterpene Lactones derived from partial charge (Q)-based fractional Accessible Surface Area Descriptors (Q_frASAs)

T. Schmidt, J. Heilmann
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引用次数: 34

Abstract

In continuation of a previous QSAR study on the cytotoxicity of 20 sesquiterpene lactones (STLs) of the helenanolide type towards a mouse tumor cell line where a very strong correlation of activity with only two indicator variables encoding the nature of the present alpha ,beta -unsatd. carbonyl structure elements (cyclopentenone and alpha -methylene-gamma -lactone structure) was found, it was the major goal of this study to establish a QSAR model for a set of STLs with wider structural variability. Cytotoxicity towards the human KB cervix carcinoma cell line was exptl. detd. for a set of 40 STLs representing five different structural groups 2 germacranolides, 6 guaianolides, 23 pseudoguaianolides, 8 eudesmanolides and 1 carabranolide (cyclopropane type xanthanolide) and the resulting IC50 values were submitted to a QSAR study using the mol. modeling program MOE. As major result it could be shown that variance in STL cytotoxicity data can be explained to a high degree by electronic and surface properties. QSAR models of considerable internal and external predictivity could be obtained by PCR and PLS anal. of a descriptor set representing fractional accessible mol. surface areas (Q_frASAs). This set of descriptors is calcd. by partitioning the mol. surface accessible to a spheric probe of radius 1.4 .ANG. into fractions attributable to atoms within 14 charge intervals from -0.3 to 0.3 e. The applicability of such Q_frASA descriptors is validated by anal. of several sets of literature data, yielding QSAR models of good statistical quality. It is therefore assumed that Q_frASA descriptors may be of wider applicability in QSAR and QSPR.
基于部分电荷(Q)的分数可及表面积描述符(Q_frASAs)衍生倍半萜内酯的定量结构-细胞毒性关系
在之前的QSAR研究中,对helenanolide型的20倍半萜内酯(STLs)对小鼠肿瘤细胞系的细胞毒性进行了研究,其中只有两个指标变量编码了目前α, β -unsatd的性质,其活性与α和β -unsatd的性质具有很强的相关性。发现羰基结构元素(环戊酮和α -亚甲基- γ -内酯结构),为一组结构变异性较大的stl建立QSAR模型是本研究的主要目标。研究了对人KB宫颈癌细胞系的细胞毒性。鉴定。对于代表5个不同结构基团的40个stl, 2个大麦果内酯,6个木聚糖内酯,23个假木聚糖内酯,8个木聚糖内酯和1个鹿角苷内酯(环丙型黄乙醇内酯),使用摩尔建模程序MOE将所得IC50值提交给QSAR研究。主要结果表明,STL细胞毒性数据的差异可以在很大程度上用电子和表面性质来解释。通过PCR和PLS分析可以得到具有较强内部和外部预测能力的QSAR模型。描述符集合表示分数可达摩尔表面积(Q_frASAs)。这组描述符被称为。通过划分一个半径为1.4 ang的球形探针可以接近的摩尔表面。在-0.3 ~ 0.3 e的14个电荷间隔内,将Q_frASA描述符的适用性进行了验证。对几组文献数据进行分析,得出统计质量良好的QSAR模型。因此,假设Q_frASA描述符在QSAR和QSPR中可能具有更广泛的适用性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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