Li Xiao, Li Ning, Sui Zhenyu, Bi Kaishun, Li Zuojing
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
School of Chinese Traditional Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.
Molecules. 2017 Feb 27;22(3):363. doi: 10.3390/molecules22030363.
Diterpenoid alkaloids are extracted from plants. These compounds have broad biological activities, including effects on the cardiovascular system, anti-inflammatory and analgesic actions, and anti-tumor activity. The anti-inflammatory activity was determined by carrageenan-induced rat paw edema and experimental trauma in rats. The number of studies focused on the determination, quantitation and pharmacological properties of these alkaloids has increased dramatically during the past few years. In this work we built a dataset composed of 15 diterpenoid alkaloid compounds with diverse structures, of which 11 compounds were included in the training set and the remaining compounds were included in the test set. The quantitative chemistry parameters of the 15 diterpenoid alkaloids compound were calculated using the HyperChem software, and the quantitative structure-activity relationship (QSAR) of these diterpenoid alkaloid compounds were assessed in an anti-inflammation model based on half maximal effective concentration () measurements obtained from rat paw edema data. The QSAR prediction model is as follows: log ( E C 50 ) = - 0.0260 × SAA + 0.0086 × SAG + 0.0011 × VOL - 0.0641 × HE - 0.2628 × LogP - 0.5594 × REF - 0.2211 × POL - 0.1964 × MASS + 0.088 × BE + 0.1398 × HF (² = 0.981, ² = 0.92). The validated consensus for the QSAR model, developed from the rat paw edema anti-inflammation model used in this study, indicate that this model was capable of effective prediction and can be used as a reliable computational predictor of diterpenoid alkaloid activity.
二萜生物碱是从植物中提取的。这些化合物具有广泛的生物活性，包括对心血管系统的作用、抗炎和镇痛作用以及抗肿瘤活性。通过角叉菜胶诱导的大鼠足爪肿胀和大鼠实验性创伤来测定抗炎活性。在过去几年中，专注于这些生物碱的测定、定量和药理特性的研究数量急剧增加。在这项工作中，我们构建了一个由15种结构各异的二萜生物碱化合物组成的数据集，其中11种化合物包含在训练集中，其余化合物包含在测试集中。使用HyperChem软件计算了这15种二萜生物碱化合物的定量化学参数，并基于从大鼠足爪肿胀数据获得的半数有效浓度（）测量值，在抗炎模型中评估了这些二萜生物碱化合物的定量构效关系（QSAR）。QSAR预测模型如下：log（EC50）= - 0.0260×SAA + 0.0086×SAG + 0.0011×VOL - 0.0641×HE - 0.2628×LogP - 0.5594×REF - 0.2211×POL - 0.1964×MASS + 0.088×BE + 0.1398×HF（² = 0.981，² = 0.92）。从本研究中使用的大鼠足爪肿胀抗炎模型开发的QSAR模型的验证共识表明，该模型能够进行有效预测，可作为二萜生物碱活性的可靠计算预测指标。
