title: An Investigation on the Quantitative Structure-Activity Relationships of the Anti-Inflammatory Activity of Diterpenoid Alkaloids.
abstract: 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 (EC50) 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 (R² = 0.981,Q² = 0.92). The validated consensusEC50for 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.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China. xiao6615@163.com.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Chinese Traditional Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China. liningsypharm@163.com.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China. iamdanielsui@126.com.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Sui
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China. kaishunbi.syphu@gmail.com.
authors.forename: Kaishun
authors.initials: K
authors.lastname: Bi
authors.affiliation: School of Medical Devices, Shenyang Pharmaceutical University, Shenyang 110016, China. Zuojing1006@hotmail.com.
authors.forename: Zuojing
authors.initials: Z
authors.lastname: Li
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology; D002351:Carrageenan / Q000009:adverse effects*; D003198:Computer Simulation; D062313:Databases, Pharmaceutical; D004195:Disease Models, Animal; D004224:Diterpenes / Q000737:chemistry* / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D051381:Rats
chemical_list: D000470:Alkaloids; D000893:Anti-Inflammatory Agents; D004224:Diterpenes; D010936:Plant Extracts; D002351:Carrageenan
keywords: anti-inflammatory; diterpenoid alkaloids; quantitative structure-activity relationship (QSAR)